Pesticidal compositions and processes related thereto

ABSTRACT

This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Nematoda, Arthropoda, and/or Mollusca, processes to produce such molecules and intermediates used in such processes, compositions containing such molecules, and processes of using such molecules against such pests. These molecules may be used, for example, as nematicides, acaricides, insecticides, miticides, and/or molluscicides. This document discloses molecules having the following formula

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of, and claims the benefit of, U.S.non-provisional application Ser. No. 14/733,057, now allowed, which wasfiled on 8 Jun. 2015, which claims the benefit of, and priority from,U.S. provisional application Ser. No. 62/009,448, which was filed on 9Jun. 2014. The entire disclosures of these applications is herebyincorporated by reference into this application.

FIELD OF THE DISCLOSURE

The invention disclosed in this document is related to the field ofprocesses to produce molecules that are useful as pesticides (e.g.,acaricides, insecticides, molluscicides, and nematicides), suchmolecules, and processes of using such molecules to control pests.

BACKGROUND OF THE DISCLOSURE

Pests cause millions of human deaths around the world each year.Furthermore, there are more than ten thousand species of pests thatcause losses in agriculture. The world-wide agricultural losses amountto billions of U.S. dollars each year.

Termites cause damage to all kinds of private and public structures. Theworld-wide termite damage losses amount to billions of U.S. dollars eachyear.

Stored food pests eat and adulterate stored food. The world-wide storedfood losses amount to billions of U.S. dollars each year, but moreimportantly, deprive people of needed food.

There is an acute need for new pesticides. Certain pests are developingresistance to pesticides in current use. Hundreds of pest species areresistant to one or more pesticides. The development of resistance tosome of the older pesticides, such as DDT, the carbamates, and theorganophosphates, is well known. But resistance has even developed tosome of the newer pesticides, for example, imidacloprid.

Therefore, for many reasons, including the above reasons, a need existsfor new pesticides.

DeMassey et al. discloses the following structure. For more detail,refer to US 2002/0068838.

Definitions

The examples given in the definitions are generally non-exhaustive andmust not be construed as limiting the invention disclosed in thisdocument. It is understood that a substituent should comply withchemical bonding rules and steric compatibility constraints in relationto the particular molecule to which it is attached.

“Alkenyl” means an acyclic, unsaturated (at least one carbon-carbondouble bond), branched or unbranched, substituent consisting of carbonand hydrogen, for example, vinyl, allyl, butenyl, pentenyl, and hexenyl.

“Alkenyloxy” means an alkenyl further consisting of a carbon-oxygensingle bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.

“Alkoxy” means an alkyl further consisting of a carbon-oxygen singlebond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy,isobutoxy, and tert-butoxy.

“Alkyl” means an acyclic, saturated, branched or unbranched, substituentconsisting of carbon and hydrogen, for example, methyl, ethyl, (C₃)alkylwhich represents n-propyl and isopropyl), (C₄)alkyl which representsn-butyl, sec-butyl, isobutyl, and tert-butyl.

“Alkynyl” means an acyclic, unsaturated (at least one carbon-carbontriple bond), branched or unbranched, substituent consisting of carbonand hydrogen, for example, ethynyl, propargyl, butynyl, and pentynyl.

“Alkynyloxy” means an alkynyl further consisting of a carbon-oxygensingle bond, for example, pentynyloxy, hexynyloxy, heptynyloxy, andoctynyloxy.

“Aryl” means a cyclic, aromatic substituent consisting of hydrogen andcarbon, for example, phenyl, naphthyl, and biphenyl.

“Cycloalkenyl” means a monocyclic or polycyclic, unsaturated (at leastone carbon-carbon double bond) substituent consisting of carbon andhydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl,norbornenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl,hexahydronaphthyl, and octahydronaphthyl.

“Cycloalkenyloxy” means a cycloalkenyl further consisting of acarbon-oxygen single bond, for example, cyclobutenyloxy,cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.

“Cycloalkyl” means a monocyclic or polycyclic, saturated substituentconsisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl,cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, and decahydronaphthyl.

“Cycloalkoxy” means a cycloalkyl further consisting of a carbon-oxygensingle bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy,norbornyloxy, and bicyclo[2.2.2]octyloxy.

“Halo” means fluoro, chloro, bromo, and iodo.

“Haloalkoxy” means an alkoxy further consisting of, from one to themaximum possible number of identical or different, halos, for example,fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy,trichloromethoxy, 1,1,2,2-tetrafluoroethoxy, and pentafluoroethoxy.

“Haloalkyl” means an alkyl further consisting of, from one to themaximum possible number of, identical or different, halos, for example,fluoromethyl, trifluoromethyl, 2,2-difluoropropyl, chloromethyl,trichloromethyl, and 1,1,2,2-tetrafluoroethyl.

“Heterocyclyl” means a cyclic substituent that may be fully saturated,partially unsaturated, or fully unsaturated, where the cyclic structurecontains at least one carbon and at least one heteroatom, where saidheteroatom is nitrogen, sulfur, or oxygen. In the case of sulfur, thatatom can be in other oxidation states such as a sulfoxide and sulfone.Examples of aromatic heterocyclyls include, but are not limited to,benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl,benzothienyl, benzothiazolyl, cinnolinyl, furanyl, imidazolyl,indazolyl, indolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl,oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl,quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl,triazinyl, and triazolyl. Examples of fully saturated heterocyclylsinclude, but are not limited to, piperazinyl, piperidinyl, morpholinyl,pyrrolidinyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl andtetrahydropyranyl. Examples of partially unsaturated heterocyclylsinclude, but are not limited to, 1,2,3,4-tetrahydroquinolinyl,4,5-dihydro-oxazolyl, 4,5-dihydro-1H-pyrazolyl, 4,5-dihydro-isoxazolyl,and 2,3-dihydro-[1,3,4]-oxadiazolyl.

Additional examples include the following

DETAILED DESCRIPTION OF THE DISCLOSURE

This document discloses molecules having the following formula (“FormulaOne”):

wherein:

(a) R1, R2, R3, R4, and R5, are, each independently, H, F, Cl, Br, I,CN, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, or (C₁-C₆)haloalkoxy;

(b) R6 is (C₁-C₆)haloalkyl;

(c) R7 is H;

(d) R8 is H, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl;

(e) R9 is H, F, Cl, Br, I, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl;

(f) R10 is F, Cl, Br, I, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl;

(g) R11 and R12 are, each independently, H, F, Cl, Br, I, (C₁-C₆)alkyl,or (C₁-C₆)haloalkyl;

(h) L is

-   -   (1) a linker that is a bond connecting the two nitrogen atoms,        or    -   (2) a (C₁-C₆)alkyl that is optionally substituted with one or        more substituents, wherein each substituent is independently        selected from F, Cl, Br, I, CN, OH, oxo, (C₁-C₆)alkoxy,        S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, and        N((C₁-C₆)alkyl)₂ wherein each (C₁-C₆)alkyl is independently        selected, and wherein each said alkyl or alkoxy has one or more        substituents independently selected from H, F, Cl, Br, and I;

(i) R13 is

-   -   (1) an H, or    -   (2) a (C₁-C₆)alkyl that is optionally substituted with one or        more substituents, wherein each substituent is independently        selected from F, Cl, Br, I, CN, OH, oxo, (C₁-C₆)alkoxy,        S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, and        N((C₁-C₆)alkyl)₂ wherein each (C₁-C₆)alkyl is independently        selected, and wherein each said alkyl or alkoxy has one or more        substituents independently selected from H, F, Cl, Br, and I;        and

(j) R14 is independently selected from (C₁-C₈)alkyl, (C₁-C₈)haloalkyl,(C₃-C₈)cycloalkyl, (C₂-C₈)alkenyl, or (C₂-C₈)alkynyl, wherein each saidalkyl, haloalkyl, cycloalkyl, alkenyl, and alkynyl has one or moresubstituents selected from F, Cl, Br, I, CN, NO₂, OH, oxo,(C₁-C₆)alkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, andN((C₁-C₆)alkyl)₂ wherein each (C₁-C₆)alkyl is independently selected,and wherein each said alkyl or alkoxy has one or more substituentsindependently selected from H, F, Cl, Br, and I.

In another embodiment of this invention R1 is H. This embodiment may beused in combination with the other embodiments of R2, R3, R4, R5, R6,R7, R8, R9, R10, R11, R12, R13, R14, and L.

In another embodiment of this invention R2 is CI or Br. This embodimentmay be used in combination with the other embodiments of R1, R3, R4, R5,R6, R7, R8, R9, R10, R11, R12, R13, R14, and L.

In another embodiment of this invention R3 is H, F, Cl, or Br. Thisembodiment may be used in combination with the other embodiments of R1,R2, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, and L.

In another embodiment of this invention R4 is CI or Br. This embodimentmay be used in combination with the other embodiments of R1, R2, R3, R5,R6, R7, R5, R9, R10, R11, R12, R13, R14, and L.

In another embodiment of this invention R5 is H. This embodiment may beused in combination with the other embodiments of R1, R2, R3, R4, R6,R7, R8, R9, R10, R11, R12, R13, R14, and L.

In another embodiment of this invention R2, R3, and R4 are CI. Thisembodiment may be used in combination with the other embodiments of R1,R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, and L.

In another embodiment of this invention R1 and R5 are H. This embodimentmay be used in combination with the other embodiments of R2, R3, R4, R6,R7, R8, R9, R10, R11, R12, R13, R14, and L.

In another embodiment of this invention R1 and R5 are H, and R2, R3, andR4 are CI. This embodiment may be used in combination with the otherembodiments of R6, R7, R8, R9, R10, R11, R12, R13, R14, and L.

In another embodiment of this invention R6 is CF₃. This embodiment maybe used in combination with the other embodiments of R1, R2, R3, R4, R5,R7, R5, R9, R10, R11, R12, R13, R14, and L.

In another embodiment of this invention R7 H. This embodiment may beused in combination with the other embodiments of R1, R2, R3, R4, R5,R6, R5, R9, R10, R11, R12, R13, R14, and L.

In another embodiment of this invention R8 is H. This embodiment may beused in combination with the other embodiments of R1, R2, R3, R4, R5,R6, R7, R9, R10, R11, R12, R13, R14, and L.

In another embodiment of this invention R9 is H. This embodiment may beused in combination with the other embodiments of R1, R2, R3, R4, R5,R6, R7, R8, R10, R11, R12, R13, R14, and L.

In another embodiment of this invention R10 is Br, CH₃, or CF₃. Thisembodiment may be used in combination with the other embodiments of R1,R2, R3, R4, R5, R6, R7, R8, R9, R11, R12, R13, R14, and L.

In another embodiment of this invention R11 is H. This embodiment may beused in combination with the other embodiments of R1, R2, R3, R4, R5,R6, R7, R8, R9, R10, R12, R13, R14, and L.

In another embodiment of this invention R12 is H. This embodiment may beused in combination with the other embodiments of R1, R2, R3, R4, R5,R6, R7, R8, R9, R10, R11, R13, R14, and L.

In another embodiment L is —CH₂—, —CH(CH₃)—, —CH(CH₂CH₃)—, or —CH₂CH₂—.This embodiment may be used in combination with the other embodiments ofR1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, and R14.

In another embodiment of this invention R13 is H or CH₃. This embodimentmay be used in combination with the other embodiments of R1, R2, R3, R4,R5, R6, R7, R8, R9, R10, R11, R12, R14, and L.

In another embodiment of this invention R14 is (C₁-C₆)alkyl or(C₃-C₆)cycloalkyl that is substituted with one or more substituentsselected from CN, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, andS(O)₂(C₁-C₆)alkyl. This embodiment may be used in combination with theother embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12,R13, and L.

In another embodiment of this invention R14 is CF₃, CH₂CF₃, CH₂CH₂CF₃,CH₂CH₂CH₂CF₃, CH₂CH₂CH(CF₃)CH₃, CH(CH₃)CH₂CF₃, C(CH₃)₂CF₃,C(CH₃)₂CH₂CF₃, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH₂CH₂CH₂CH₃, CH₂CH₂CH₂CH₂CH₃,CH(CH₃)₂, CH₂CH(CH₃)₂, CH₂CH₂CH(CH₃)₂, C(CH₃)₃, CH₂C(CH₃)₃,CH₂CH₂C(CH₃)₃, CH₂CH₂CH₂C(CH₃)₃, cyclopropyl, CH═CH₂, CH═CH(CH₃),CH═C(CH₃)₂, CH₂CH═CH₂, CH₂CH═CH(CH₃), C(CH₃)═CH₂, C(CH₃)═CH(CH₃), C═CH,CH₂C═CH, CH₂CN, CH₂CH₂CN, CH₂SCH₃, CH₂CH₂SCH₃, CH₂S(O)CH₃,CH₂CH₂S(O)CH₃, CH₂S(O)₂CH₃, CH₂CH₂S(O)₂CH₃. This embodiment may be usedin combination with the other embodiments of R1, R2, R3, R4, R5, R6, R7,R8, R9, R10, R11, R12, R13, and L.

In another embodiment of this invention:

(a) R1 is H;

(b) R2 is H, F, Cl, or Br;

(c) R3 is H, F, Cl, or Br;

(d) R4 is H, F, Cl, or Br;

(e) R5 is H;

(f) R6 is (C₁-C₈)haloalkyl;

(g) R7 is H;

(h) R8 is H;

(i) R9 is H;

(j) R10 is selected from a group consisting of F, Cl, Br, I,(C₁-C₆)alkyl, and

(C₁-C₆)haloalkyl;

(k) R11 is H;

(l) R12 is H;

(m) L is

-   -   (1) a linker that is bond connecting the two nitrogen atoms, or    -   (2) a (C₁-C₆)alkyl;

(n) R13 is

-   -   (1) an H, or    -   (2) a (C₁-C₈)alkyl;

(o) R14 is independently selected from (C₁-C₈)alkyl, (C₁-C₈)haloalkyl,(C₃-C₈)cycloalkyl, (C₂-C₈)alkenyl, or (C₂-C₈)alkynyl, wherein each saidalkyl, haloalkyl, cycloalkyl, alkenyl, and alkynyl has one or moresubstituents selected from F, Cl, Br, I, CN, NO₂, OH, oxo,(C₁-C₆)alkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, andN((C₁-C₆)alkyl)₂ wherein each (C₁-C₆)alkyl is independently selected,and wherein each said alkyl or alkoxy has one or more substituentsindependently selected from H, F, Cl, Br, and I.

In another embodiment of this invention:

(a) R1 is H;

(b) R2 is Cl or Br;

(c) R3 is H, F, Cl, or Br;

(d) R4 is Cl or Br;

(e) R5 is H;

(f) R6 is (C₁-C₈)haloalkyl;

(g) R7 is H;

(h) R8 is H;

(i) R9 is H;

(j) R10 is Br, (C₁-C₈)alkyl, (C₁-C₈)haloalkyl;

(k) R11 is H;

(l) R12 is H;

(m) L is

-   -   (1) a linker that is bond connecting the two nitrogen atoms, or    -   (2) a (C₁-C₆)alkyl;

(n) R13 is

-   -   (1) an H, or    -   (2) a (C₁-C₈)alkyl;

(o) R14 is (C₁-C₈)alkyl, (C₁-C₈)haloalkyl, (C₃-C₈)cycloalkyl, or(C₂-C₈)alkenyl, wherein each said alkyl or cycloalkyl is substitutedwith CN, SCH₃, S(O)CH₃, or S(O)₂CH₃.

Preparation of Benzyl Bromides

Benzyl alcohol 1-3, wherein R1, R2, R3, R4, R5, R6, and R7 are aspreviously disclosed, may be prepared in several ways. Treatment ofketones 1-1, wherein R1, R2, R3, R4, R5, and R6 are as previouslydisclosed with a reducing agent, such as sodium borohydride, in thepresence of a base, such as aqueous sodium hydroxide, in a polar proticsolvent, such as methanol at about −10° C. to about 10° C. to providebenzyl alcohol 1-3 (Scheme 1, step a). Alternatively, aldehydes 1-2,wherein R1, R2, R3, R4, R5, and R7 are as previously disclosed, may beallowed to react with trifluorotrimethylsilane in the presence of acatalytic amount of tetrabutylammonium fluoride in a polar aproticsolvent, such as tetrahydrofuran (Scheme 1, step b) to provide benzylalcohol 1-3. Subsequently, benzyl alcohol 1-3 may be converted intobenzyl halide 1-4, wherein Y is Br, Cl, or I, and R1, R2, R3, R4, R5,R6, and R7 are as previously disclosed, by treatment with a halogenatingreagent, such as N-bromosuccinimide, and triethylphosphite in anon-reactive solvent, such as dichloromethane at about 40° C. to providebenzyl halide 1-4, Y is Br; or such as thionyl chloride, and pyridine ina hydrocarbon solvent, such as toluene at about 110° C. to providebenzyl halide 1-4, where Y is Cl (Scheme 1, step c).

Preparation of Vinylbenzoic Acids and Esters

Halobenzoic acids 2-1, wherein R9, R10, R11, and R12 are as previouslydisclosed may be converted to vinylbenzoic acid ester 2-3, wherein R8,R9, R10, R11, and R12 are as previously disclosed or vinylbenzoic acids2-4, wherein R8, R9, R10, R11, and R12 are as previously disclosed.Halobenzoic acid 2-1, may be treated with a base, such as n-butylithium,and dimethylformamide in a polar, aprotic solvent, such astetrahydrofuran, at a temperature of about −78° C. (Scheme 2, step a).The resulting formyl benzoic acid may be treated with an acid, such assulfuric acid, in the presence of an alcohol, such as ethyl alcohol, toprovide formyl benzoic acid ethyl ester 2-2 (Scheme 2, step b). Vinylbenzoic acid ester 2-3 may be accessed via reaction of 2-2, with a base,such as potassium carbonate, and methyl triphenylphosphonium bromide ina polar aprotic solvent, such as 1,4-dioxane, at about ambienttemperature (Scheme 2, step c). Alternatively, halobenzoic acid 2-1 maybe treated with di-tert-butyl dicarbonate in the presence of a base,such as triethylamine and a catalytic amount of4-(dimethylamino)pyridine in a polar aprotic solvent, such astetrahydrofuran, at about ambient temperature (Scheme 2, step d). Theresulting benzoic acid tert-butyl ester may be treated with vinylboronic anhydride pyridine complex in the presence of a palladiumcatalyst, such a tetrakis(triphenylphospine)palladium(0), and a base,

such as potassium carbonate, in a non-reactive solvent such as tolueneat about 110° C. to provide vinyl benzoic acid ester 2-3 (Scheme 2, stepe).

Halobenzoic acid 2-1 may be treated directly with a vinyltrifluoroboratein the presence of a palladium catalyst, such as[1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II) and a base,such as potassium carbonate, in a non-reactive solvent such asdimethylsulfoxide at temperatures ranging from about 80° C. to about140° C., to provide vinyl benzoic acids 2-4 (Scheme 2, step f).

Preparation of Diphenyl Allylbenzoic Acids

Benzyl halides 1-4 and vinylbenzoic acid esters 2-3 may be treated withcopper(I) chloride and 2,2-bipyridyl in a solvent, such as1,2-dichlorobenzene, at a temperature of about 180° C. to providediphenyl allylbenzoic esters 3-1, wherein R1, R2, R3, R4, R5, R6, R7,R8, R9, R10, R11, and R12 are as previously disclosed (Scheme 3, stepa). Diphenyl allylbenzoic esters 3-1 may be then converted to diphenylallylbenzoic acids 3-2, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10,R11, and R12 are as previously disclosed. Treatment of diphenylallylbenzoic esters 3-1, with an acid, such as about 11 N aqueoushydrochloric acid, in a polar aprotic solvent, such as 1,4-dioxane, atabout 100° C. may provide diphenyl allylbenzoic acids 3-2 (Scheme 3,step b).

Alternatively, benzyl halides 1-4 and vinylbenzoic acids 2-4 may betreated with copper(I) chloride and 2,2-bipyridyl in a solvent, such as1,2-dichlorobenzene or N-methylpyrolidine, at temperatures between about60° C. and about 180° C. to provide diphenyl allylbenzoic acids 3-2(Scheme 3, step c).

Preparation of Diacylamines

Diacylamines 4-3, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11,R12, R13, R14, and L are as previously disclosed may be prepared bytreatment with acylamine salts 4-2, wherein R13, R14, and L are aspreviously disclosed, and activated carboxylic acids 4-1, wherein X isan activating group, and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11,and R12 are as previously disclosed, with a base, such as potassiumbicarbonate, triethylamine, diisopropylethylamine, or preferably4-methylmorpholine in an anhydrous aprotic solvent such asdichloromethane, tetrahydrofuran, 1,2-dichloroethane, dimethylformamide,or any combination thereof, at temperatures between about 0° C. andabout 120° C. (Scheme 4, step a).

Activated carboxylic acids 4-1 may be an acid halide, such as an acidchloride, an acid bromide, or an acid fluoride; a carboxylic ester, suchas a para-nitrophenyl ester, a pentafluorophenyl ester, an ethyl(hydroxyiminio)cyanoacetate ester, a methyl ester, an ethyl ester, abenzyl ester, an N-hydroxysuccinimidyl ester, a hydroxybenzotriazol-1-ylester, or a hydroxypyridyltriazol-1-yl ester; an O-acylisourea; an acidanhydride; or a thioester. Acid chlorides are most preferred and may beprepared from the corresponding carboxylic acids by treatment with adehydrating chlorinating reagent, such as oxalyl chloride or thionylchloride both with or without catalytic dimethylformamide. Activatedcarboxylic esters 4-1 may be prepared from carboxylic acids in situ witha uronium salt, such as1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxid hexafluorophosphate (HATU),O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate(HBTU), or(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbeniumhexafluorophosphate (COMU). Activated carboxylic esters 4-1 may also beprepared from carboxylic acids in situ with a phosphonium salt such asbenzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBop). Activated carboxylic esters 4-1 may also be prepared fromcarboxylic acids in situ with a coupling reagent such as1-(3-dimethylamino propyl)-3-ethylcarbodiimide, ordicyclohexylcarbodiimide in the presence of a triazolol such ashydroxybenzotriazole monohydrate (HOBt) or 1-hydroxy-7-azabenzotriazole(HOAt). O-Acylisoureas may be prepared with a dehydrating carbodimidesuch as 1-(3-dimethylamino propyl)-3-ethylcarbodiimide ordicyclohexylcarbodiimide.

Diacylamines 4-3, wherein R14 contains a sulfide may be oxidized to thecorresponding sulfoxide and sulfone by treatment with one equivalent ofsodium perborate in a protic solvent such as acetic acid (sulfoxide) ortwo equivalents of sodium perborate (sulfone). Preferably, the oxidationwill be performed at temperatures between about 40° C. to about 100° C.using 1.5 equivalents of sodium perborate to provide chromatographicallyseparable mixtures of sulfoxide and sulfone diacylaminals 4-3, whereinR14 contains a sulfoxide or sulfone.

Alternatively, diacylamines 5-3, wherein R1, R2, R3, R4, R5, R6, R7, R8,R9, R10, R11, R12, R14, and L are as previously disclosed may beprepared by treatment of acylamine salts 5-1, wherein R1, R2, R3, R4,R5, R6, R7, R8, R9, R10, R11, R12, and L are as previously disclosed,with activated carboxylic acids 5-2, wherein X is an activating groupand R14 is as previously disclosed, with a base, such as potassiumbicarbonate, triethylamine, diisopropylethylamine, or preferably4-methylmorpholine in an anhydrous aprotic solvent such asdichloromethane, tetrahydrofuran, 1,2-dichloroethane, dimethylformamide,or any combination thereof, at temperatures between about 0° C. andabout 120° C. (Scheme 5, step a).

Activated carboxylic acids 5-2 may be an acid halide, such as an acidchloride, an acid bromide, or an acid fluoride; a carboxylic ester, suchas a para-nitrophenyl ester, a pentafluorophenyl ester, an ethyl(hydroxyiminio)cyanoacetate ester, a methyl ester, an ethyl ester, abenzyl ester, an N-hydroxysuccinimidyl ester, a hydroxybenzotriazol-1-ylester, or a hydroxypyridyltriazol-1-yl ester; an O-acylisourea; an acidanhydride; or a thioester. Acid chlorides are most preferred and may beprepared from the corresponding carboxylic acids by treatment with adehydrating chlorinating reagent, such as oxalyl chloride or thionylchloride. Activated carboxylic esters 5-2 may be prepared fromcarboxylic acids in situ with a uronium salt, such as1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxid hexafluorophosphate (HATU),O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate(HBTU), or (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate (COMU). Activatedcarboxylic esters 5-2 may also be prepared from carboxylic acids in situwith a phosphonium salt such asbenzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBop). Activated carboxylic esters 5-2 may also be prepared fromcarboxylic acids in situ with a coupling reagent such as1-(3-dimethylamino propyl)-3-ethylcarbodiimide, ordicyclohexylcarbodiimide in the presence of a triazolol such ashydroxybenzotriazole monohydrate (HOBt) or 1-hydroxy-7-azabenzotriazole(HOAt). O-Acylisoureas may be prepared with a dehydrating carbodimidesuch as 1-(3-dimethylamino propyl)-3-ethylcarbodiimide ordicyclohexylcarbodiimide.

Carboxylic acid precursors to and activated carboxylic acids 5-2,wherein R14 contains a sulfide may be oxidized to the correspondingsulfoxide or sulfone by treatment with one equivalent of sodiumperborate in a protic solvent such as acetic acid (sulfoxide) or twoequivalents of sodium perborate (sulfone). Preferably, the oxidationwill be performed at temperatures between about 40° C. to about 100° C.using 1.5 equivalents of sodium perborate to provide chromatographicallyseparable mixtures of sulfoxide and sulfone.

Additionally, diacylamines 4-3 may be prepared by treating acylamines5-3 with an alkylating reagent R13-Z, wherein R13 is not H and is aspreviously disclosed and Z is a leaving group, such as a halogen orsulfonate, wherein R13-Z is an alkyl halide, such as iodomethane, or anactivated alcohol, such as ethyltriflate in the presence of a base, suchas sodium hydride, cesium carbonate, silver oxide, potassium hydride,tetrabutylammonium fluoride, or potassium carbonate in a polar aproticsolvent such as dimethylformamide, tetrahydrofuran, acetone,acetonitrile, dimethylsulfoxide, or glyme. Alternatively, the alkylationof acylamines 5-3 may be conducted in a biphasic manner using an alkalimetal hydroxide base, such as sodium hydroxide, in water, aphase-transfer catalysts, such as a tetraalkylammonium salt, in anorganic solvent such as toluene or dichloromethane at temperaturesranging from about 0° C. and about 120° C. (Scheme 6, step a).

Diacylamines 5-3, wherein R14 contains a sulfide may be oxidized to thecorresponding sulfoxide and sulfone by treatment with one equivalent ofsodium perborate in a protic solvent such as acetic acid (sulfoxide) ortwo equivalents of sodium perborate (sulfone). Preferably, the oxidationwill be performed at temperatures between about 40° C. to about 100° C.using 1.5 equivalents of sodium perborate to provide chromatographicallyseparable mixtures of sulfoxide and sulfone diacylamines 5-3, whereinR14 contains a sulfoxide or sulfone.

Preparation of Acylamine Salt 5-1 Precursors

Amides 7-2, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12,and L are as previously disclosed are novel intermediates which may beused in the preparation of acylamine salts 5-1. Amides 7-2 may beprepared by reacting alpha-amino amides 7-1, wherein L is as previouslydisclosed, and an activated carboxylic acid 4-1 with a base, such aspotassium bicarbonate, triethylamine, diisopropylethylamine, orpreferably 4-methylmorpholine in an anhydrous aprotic solvent such asdichloromethane, tetrahydrofuran, 1,2-dichloroethane, dimethylformamide,or any combination thereof, at temperatures between about 0° C. andabout 120° C. (Scheme 7, step a).

Preparation of Acylamine Salts 5-1

Acylamines 5-1 may be prepared from amides 7-2 by conversion of theprimary amide nitrogen to a nitrene-like species, resulting in nitrogenmigration, followed by isocyanate formation. Hydrolysis of theintermediate isocyanate with aqueous acid, such as hydrochloric acid mayprovide acylamine salts 5-1 (Scheme 8, step a). When an acid weaker thanaqueous hydrochloric acid is employed, anion exchange may be achieved bytreatment with hydrochloric acid to provide acylamine salts 5-1.Preferably amide 7-2 may be treated with iodobenzenebis(trifluoroacetate) in a solvent mixture consisting of about two partsacetonitrile and about one part deionized water at temperatures betweenabout 0° C. and about 120° C. The resulting trifluoroacetate salt may beconverted to the chloride salt by the addition of hydrochloric acidfollowed by evaporation of volatiles.

Preparation of Acylamine Salts 4-2

Acylamine salts 4-2 may be prepared according to those reactionsoutlined in Scheme 9, Scheme 10, and Scheme 11. Treatment carboxylicacids 9-1, wherein X is OH, and R13, R14, and L are as previouslydisclosed, or the corresponding activated acids 9-1, wherein X is anactivating group as previously described may be reacted with a nitrogennucleophile to provide amides and amide derivatives 9-2, wherein Y2 isH, N₂, NH tert-butoxycarbonyl, or OH) and R13, R14, and L are aspreviously disclosed. The resultant amides and amide derivatives 9-2 maybe converted to acylamine salts 4-2 by the formation of thecorresponding nitrene-like species, resulting in nitrogen migration, andsubsequent hydrolysis of the resultant isocyanate.

Activated amido acids 9-1, wherein X, R13, R14, and L are as previouslydisclosed, may be treated with ammonia (Scheme 9, step a) to providecarboxamides 9-2, wherein Y2 is H. Carboxamides 9-2, wherein Y2 is H,may be converted to acylamine 4-2 via the Hoffman rearrangement followedby acidification with hydrochloric acid or preferably by treatment withiodobenzene bis(trifluoroacetate) in a solvent mixture consisting ofabout one part acetonitrile and about one part deionized water attemperatures between about 0° C. and about 120° C. (Scheme 9, step e).The resulting trifluoroacetate salt may be converted to the chloridesalt by the addition of hydrochloric acid followed by evaporation ofvolatiles.

Amido acids 9-1, wherein X is OH, and R13, R14, and L are as previouslydisclosed, may be treated with an azide source such asdiphenylphosphoryl azide in the presence of a base, such as protonsponge or triethylamine (Scheme 9, step b) to provide acyl azides 9-2,wherein Y2 is N₂. Alternatively, activated amido acids 9-1, wherein X isas described above, may be treated with an azide source, such as sodiumazide (Scheme 9, step b) to provide acyl azides 9-2, wherein Y2 is N₂.Acyl azides 9-2, may be heated to about 40° C. to about 110° C. in anaprotic solvent, such as acetonitrile, toluene, 1,2-dichloroethane,tetrahyrofuran, or 1,4-dioxane to affect a Curtius Rearrangementresulting in the formation of a non-isolated isocyanate that may betreated with aqueous hydrochloric acid to provide acylamine salts 4-2.Alternatively, the isocyanate may be treated with an alcohol, such astert-butanol, para-methoxy benzyl alcohol, or benzyl alcohol to providean acid labile carbamate, which after purification may be decomposedunder acidic conditions to provide acylamine salts 4-2 (Scheme 9, stepf).

Activated amido acids 9-1, wherein X, R13, R14, and L are as previouslydisclosed, may be treated with protected hydrazines (Scheme 9, step c),such as tert-butyl carbazate in the presence of a base, such as4-methylmorpholine, to provide protected hydrazides 9-2, wherein Y2 isNH tert-butoxycarbonyl. Protected hydrazides 9-2 may be deprotected bytreatment with acids such as hydrochloric acid or trifluoroacetic acidin aprotic solvents such as 1,4-dioxane or dichloromethane. Theresulting hydrazide salts 9-2, wherein Y2 is NH₃Cl, may be neutralizedto provide hydrazide 9-2, wherein Y2 is NH₂. Hydrazides 9-2 may then bediazotized with reagents such as nitric acid or isobutyl nitrite toproduce isocyanates that may be converted to acylamine salts 4-2 (Scheme9, step g).

Activated amido acids 9-1, wherein X, R13, R14, and L are as previouslydisclosed, may be treated with hydroxylamine (Scheme 9, step d) toprovide hydroxamic acids 9-2, wherein Y2 is OH. Hydroxamic acids 9-2 maybe acylated with activated carboxylic acids, wherein activatedcarboxylic acids are as previously disclosed, to provide the O-acylhydroxamic acids 9-2, wherein Y2 is O-acyl, which may be converted toisocyanates by treatment with heat or the addition of base to produceisocyanates that may be converted to acylamine salts 4-2 (Scheme 9, steph).

Carbamate acids 10-1, wherein R13 and L are as previously disclosed, maybe treated with an alkylating reagent R13-Z, wherein R13 is not H and isas previously disclosed and Z is a leaving group, such as a halogen orsulfonate, wherein R13-Z is an alkyl halide, such as iodomethane, or anactivated alcohol, such as ethyltriflate, in the presence of a base,such as sodium hydride, cesium carbonate, silver oxide, potassiumhydride, tetrabutylammonium fluoride, or potassium carbonate in a polaraprotic solvent such as dimethylformamide, tetrahydrofuran, acetone,acetonitrile, dimethylsulfoxide, or glyme. Alternatively, the alkylationof carbamate acids 10-1 may be conducted in a biphasic manner using analkali metal hydroxide base, such as sodium hydroxide, in water, aphase-transfer catalysts, such as a tetraalkylammonium salt, in anorganic solvent such as toluene or dichloromethane at temperaturesranging from about 0° C. to about 120° C. (Scheme 10, step a).

The resultant carbamate acids 10-2, wherein R13 and L are as previouslydisclosed may be treated with an azide source such as diphenylphosphorylazide in the presence of a base, such as proton sponge or triethylamine(Scheme 10, step b) to provide an acyl azide which may in turn be heatedfrom about 40° C. to about 110° C. in an aprotic solvent, such asacetonitrile, toluene, 1,2-dichloroethane, tetrahydrofuran, or1,4-dioxane to effect a Curtius Rearrangement resulting in the formationof an isocyanate (Scheme 10, step c). Treatment of the resultantisocyanate with benzyl alcohol may provide a differentially protecteddicarbamate (Scheme 10, step d). Deprotection of the tert-butylcarbamatemay be achieved by treatment with an acid, such as hydrochloric acid ortrifluoroacetic acid, in a polar aprotic solvent, such as 1,4-dioxane ordichloromethane, at temperatures between about 0° C. and about 65° C.,to provide benzyl carbamate amine salts 10-3, wherein R13 and L are aspreviously disclosed (Scheme 10, step e).

Benzyl carbamate amine salts 10-3 may treated with activated carboxylicacids 5-2 in the presence of a base, such as potassium bicarbonate,triethylamine, diisopropylethylamine, or preferably 4-methylmorpholinein an anhydrous aprotic solvent such as dichloromethane,tetrahydrofuran, 1,2-dichloroethane, dimethylformamide, or anycombination thereof, at temperatures between about 0° C. and about 120°C. (Scheme 10, step f). The resultant carbamate acylamine may be treatedwith a source of hydrogen and a transition metal catalyst, such aspalladium on carbon to provide acylamine salts 4-2 (Scheme 10, step g).

Carbamate acids 10-1 may be treated with an alkylating reagent R15-Z,wherein R15 is (C₁-C₈)alkenyl and Z is a leaving group, such as ahalogen or a sulfonate, wherein R15-Z is an alkenyl halide, such asallyl bromide, or an activated alcohol, such as crotyltriflate in thepresence of a base, such as sodium hydride, cesium carbonate, silveroxide, potassium hydride, tetrabutylammonium fluoride, or potassiumcarbonate in a polar aprotic solvent such as dimethylformamide,tetrahydrofuran, acetone, acetonitrile, dimethylsulfoxide, or glyme.Alternatively, the alkylation of amido esters 10-1 may be conducted in abiphasic manner using an alkali metal hydroxide base, such as sodiumhydroxide, in water, a phase-transfer catalysts, such as atetraalkylammonium salt, in an organic solvent such as toluene ordichloromethane at temperatures ranging from about 0° C. to about 100°C. (Scheme 11, step a).

The resultant carbamate acids 11-2, wherein R15 and L are as previouslydisclosed may be treated with an azide source such as diphenylphosphorylazide in the presence of a base, such as proton sponge or triethylamine(Scheme 11, step b) to provide an acyl azide which may in turn be heatedto about 40° C. to about 110° C. in an aprotic solvent, such asacetonitrile, toluene, 1,2-dichloroethane, tetrahydrofuran, or1,4-dioxane to effect a Curtius Rearrangement resulting in the formationof an isocyanate (Scheme 11, step c). Treatment of the resultantisocyanate with benzyl alcohol may provide a differentially protecteddicarbamate (Scheme 11, step d). Deprotection of the tert-butylcarbamatemay be achieved by treatment with an acid, such as hydrochloric acid ortrifluoroacetic acid, in a polar aprotic solvent, such as 1,4-dioxane ordichloromethane, at temperatures between about 0° C. and about 65° C.,to provide benzyl carbamate aminal salts 11-3, wherein L and R15 are aspreviously disclosed (Scheme 11, step e).

Benzyl carbamate amine salts 11-3 may be treated with activatedcarboxylic acids 5-2 in the presence of a base, such as potassiumbicarbonate, triethylamine, diisopropylethylamine, or preferably4-methylmorpholine in an anhydrous aprotic solvent such asdichloromethane, tetrahydrofuran, 1,2-dichloroethane, dimethylformamide,or any combination thereof, at temperatures between about 0° C. andabout 120° C. (Scheme 11, step f). The resultant carbamate acylaminalmay be treated with a source of hydrogen and a transition metalcatalyst, such as palladium on carbon to provide acylamine salts 4-2(Scheme 11, step g).

Preparation of Amido Acids 9-1

Amido esters 12-2, wherein R13 and L are as previously disclosed may beprepared by treating amino esters 12-1, wherein Y3 is O(C₁-C₈)alkyl orO(C₁-C₈)alkylphenyl and L is as previously disclosed, with activatedcarboxylic acids 5-2 with a base, such as potassium bicarbonate,triethylamine, diisopropylethylamine, or preferably 4-methylmorpholinein an anhydrous aprotic solvent such as dichloromethane,tetrahydrofuran, 1,2-dichloroethane, dimethylformamide, or anycombination thereof, at temperatures between about 0° C. and about 120°C. (Scheme 12, step a).

Amido esters 12-2 may be treated with an alkylating reagent R13-Z,wherein R13 is not H and as previously disclosed and Z is a leavinggroup, such as a halogen or a sulfonate, wherein R13-Z is an alkylhalide, such as iodomethane or an activated alcohol, such asethyltriflate in the presence of a base, such as sodium hydride, cesiumcarbonate, silver oxide, potassium hydride, tetrabutylammonium fluoride,or potassium carbonate in a polar aprotic solvent such asdimethylformamide, tetrahydrofuran, acetone, acetonitrile,dimethylsulfoxide, or glyme. Alternatively, the alkylation of amidoesters 12-2 may be conducted in a biphasic manner using an alkali metalhydroxide base, such as sodium hydroxide, in water, a phase-transfercatalyst, such as a tetraalkylammonium salt, in an organic solvent suchas toluene or dichloromethane at temperatures ranging from about 0° C.to about 120° C. (Scheme 12, step b).

The resultant alkylated amido esters, when Y3 is O(C₁-C₈)alkyl, may betreated with an acid, such as about 11 N aqueous hydrochloric acid, in apolar aprotic solvent, such as 1,4-dioxane, at about 100° C. to provideamido acids 9-1. Alternatively, alkylated amido esters, when Y3 isO-tert-butyl, may be treated with hydrochloric acid in 1,4-dioxane.Alkylated amido esters, when Y3 is O(C₁-C₈)alkyl may be treated with analkali base, such as lithium hydroxide, in a polar solvent, such as1,4-dioxane, tetrahydrofuran, methanol, water, or mixtures thereof, attemperatures between 0° C. and about 140° C. to provide amido acids 9-1.The alkylated amido esters, when Y3 is O(C₁-C₈)alkylphenyl may betreated with a source of hydrogen and a transition metal catalyst, suchas palladium on carbon to provide amido acids 9-1 (Scheme 12, step c).

Amido acids 9-1 may be prepared in alternate sequences to the sequencediscussed above. Step b may be initially performed to providesubstituted amine esters 12-3, wherein Y3 is O(C₁-C₈)alkyl orO(C₁-C₈)alkylphenyl, and R13 and L are as previously disclosed, beforesteps a and steps c are performed to provide amido acids 9-1.

Substituted amine esters 12-3, wherein R13 is as previously disclosed,may be prepared by treating amino esters 12-1 with R16-C(O)H orR16-C(O)(C₁-C₈)alkyl, wherein R16 is not H, in the presence of areductant, such as sodium borohydride or sodium cyanoborohydride, inprotic solvents such as methanol or ethanol in the presence of weakorganic acids, such acetic acid. Alternatively, the imine intermediateresulting from condensation of the amine and the carbonyl may be reducedby a source of hydrogen and a transition metal catalyst, such aspalladium on carbon to provide substituted amine esters 12-3, when Y3 isO(C₁-C₈)alkyl (Scheme 12, step d).

Amido acids 9-1 may be prepared in a two-step sequence, by firsttreating substituted amine esters 12-3 with activated carboxylic acids5-2 with a base, such as potassium bicarbonate, triethylamine,diisopropylethylamine, or preferably 4-methylmorpholine in an anhydrousaprotic solvent such as dichloromethane, tetrahydrofuran,1,2-dichloroethane, dimethylformamide, or any combination thereof, attemperatures between about 0° C. and about 120° C. (Scheme 12, step e).

Secondly, the resultant amido esters, when Y3 is O(C₁-C₈)alkyl may betreated with an acid, such as about 11 N aqueous hydrochloric acid, in apolar aprotic solvent, such as 1,4-dioxane, at about 100° C. to provideamido acids 9-1. Alternatively, amido esters, when Y3 is Otert-butyl,may be treated with hydrochloric acid in 1,4-dioxane. Amido esters, whenY3 is O(C₁-C₈)alkyl may be treated with an alkali base, such as lithiumhydroxide, in a polar solvent, such as 1,4-dioxane, tetrahydrofuran,methanol, water, or mixtures thereof, at temperatures between 0° C. andabout 100° C. to provide amido acids 9-1. Finally, acylated amidoesters, when Y3 is O(C₁-C₈)alkylphenyl may be treated with a source ofhydrogen and a transition metal catalyst, such as palladium on carbon toprovide amido acids 9-1 (Scheme 12, step f).

Amido acids 12-2 may be prepared by treating amino esters 12-1 with anactivated carboxylic acid 5-2 with a base, such as potassiumbicarbonate, triethylamine, diisopropylethylamine, or preferably4-methylmorpholine in an anhydrous aprotic solvent such asdichloromethane, tetrahydrofuran, 1,2-dichloroethane, dimethylformamide,or any combination thereof, at temperatures between about 0° C. andabout 120° C. (Scheme 13, step a).

Amido esters 12-2 may be treated with an alkylating reagent R15-Z,wherein R15 is (C₁-C₈)alkenyl and Z is a leaving group, such as ahalogen or a sulfonate, wherein R15-Z is an alkyl halide, such as allylbromide, or an activated alcohol, such as crotyltriflate in the presenceof a base, such as sodium hydride, cesium carbonate, silver oxide,potassium hydride, tetrabutylammonium fluoride, or potassium carbonatein a polar aprotic solvent such as dimethylformamide, tetrahydrofuran,acetone, acetonitrile, dimethylsulfoxide, or glyme. Alternatively, thealkylation of amido esters 12-2 may be conducted in a biphasic mannerusing an alkali metal hydroxide base, such as sodium hydroxide, inwater, a phase-transfer catalysts, such as a tetraalkylammonium salt, inan organic solvent such as toluene or dichloromethane at temperaturesranging from about 0° C. to about 100° C. (Scheme 13, step b). Thealkene present in R15 may be subsequently reduced by a source ofhydrogen and a transition metal catalyst, such as palladium on carbon.In alkylated amido esters when Y3 is O(C₁-C₈)alkylphenyl reduction ofthe alkene may also lead to concomitant reduction of the ester toprovide amido acids 9-1 (Scheme 13, step c).

Alkylated amido esters, when Y3 is O(C₁-C₈)alkyl may be treated with anacid, such as about 11 N aqueous hydrochloric acid, in a polar aproticsolvent, such as 1,4-dioxane, at about 100° C. to provide amido acids9-1. Alternatively, amido esters, when Y3 is Otert-butyl, may be treatedwith hydrochloric acid in 1,4-dioxane. Alkylated amido esters, when Y3is O(C₁-C₈)alkyl may be treated with an alkali base, such as lithiumhydroxide, in a polar solvent, such as 1,4-dioxane, tetrahydrofuran,methanol, water, or mixtures thereof, at temperatures between 0° C. andabout 100° C. to provide amido acids 9-1 (Scheme 10, step d).

Amido acids 9-1 may be prepared in alternate sequences to the sequencediscussed above. Step b may be initially performed to providesubstituted amine esters 13-1, wherein Y3 is O(C₁-C₈)alkyl orO(C₁-C₈)alkylphenyl, and R15 and L are as previously disclosed, beforesteps a and steps c, or steps a, steps c, and steps d are performed toprovide 9-1.

EXAMPLES

The examples are for illustration purposes and are not to be construedas limiting the invention disclosed in this document to only theembodiments disclosed in these examples.

Starting materials, reagents, and solvents that were obtained fromcommercial sources were used without further purification. Anhydroussolvents were purchased as Sure/Seal™ from Aldrich and were used asreceived. Melting points were obtained on a Thomas Hoover Unimeltcapillary melting point apparatus or an OptiMelt Automated Melting PointSystem from Stanford Research Systems and are uncorrected. Molecules aregiven their known names, named according to naming programs within ISISDraw, ChemDraw, or ACD Name Pro. If such programs are unable to name amolecule, the molecule is named using conventional naming rules. ¹H NMRspectral data are in ppm (δ) and were recorded at 300, 400, or 600 MHz,and ¹³C NMR spectral data are in ppm (δ) and were recorded at 75, 100,or 150 MHz, unless otherwise stated.

Example 1: Preparation of1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (C2)

Step 1 Method A. 1-(3,5-Dichlorophenyl)-2,2,2-trifluoroethanol (C1)

To a stirred solution of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone(procured from Rieke Metals, UK; 5.00 g, 20.5 mmol) in methanol (100 mL)at 0° C. were added sodium borohydride (3.33 g, 92.5 mL) and aqueoussodium hydroxide (1 N; 10 mL). The reaction mixture was warmed to 25° C.and stirred for 2 hours. After the reaction was deemed complete by thinlayer chromatography, saturated aqueous ammonium chloride was added tothe reaction mixture, and the mixture was concentrated under reducedpressure. The residue was diluted with diethyl ether and washed withwater (3×50 mL). The organic layer was dried over sodium sulfate andconcentrated under reduced pressure to afford the title compound as aliquid (4.00 g, 79%): ¹H NMR (400 MHz, CDCl₃) δ 7.41 (m, 3H), 5.00 (m,1H), 2.74 (s, 1H); ESIMS m/z 242.97 ([M−H]⁻).

Step 1 Method B. 1-(3,5-Dichlorophenyl)-2,2,2-trifluoroethanol (C1)

To a stirred solution of 3,5-dichlorobenzaldehyde (10 g, 57 mmol) intetrahydrofuran (250 mL) were added trifluoromethyltrimethylsilane (9.8g, 69 mmol) and a catalytic amount of tetrabutylammonium fluoride. Thereaction mixture was stirred at 25° C. for 8 hours. After the reactionwas deemed complete by thin layer chromatography, the reaction mixturewas diluted with hydrochloric acid (3 N) and then was stirred for 16hours. The reaction mixture was diluted with water and was extractedwith ethyl acetate (3 times). The combined organic extracts were washedwith brine, dried over sodium sulfate, and concentrated under reducedpressure to afford the title compound as a liquid (8.4 g, 60%).

Step 2. 1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (C2)

To a stirred solution of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanol(C1) (4.00 g, 16.3 mmol) in dichloromethane (50 mL), were addedN-bromosuccinimide (2.90 g, 16.3 mmol) and triphenyl phosphite (5.06 g,16.3 mmol), and the resultant reaction mixture was heated at reflux for18 hours. After the reaction was deemed complete by thin layerchromatography, the reaction mixture was cooled to 25° C. and wasconcentrated under reduced pressure. Purification by flash columnchromatography using 100% pentane as eluent afforded the title compoundas a liquid (2.00 g, 40%): ¹H NMR (400 MHz, CDCl₃) δ 7.41 (s, 3H), 5.00(m, 1H); EIMS m/z 306 ([M]⁺).

The following compounds were made in accordance with the proceduresdisclosed in Step 1 Method A of Example 1.

1-(3,5-difluorophenyl)-2,2,2-trifluoroethanol (C3)

The product was isolated as a colorless oil (0.2 g, 75%): ¹H NMR (400MHz, CDCl₃) δ 7.05 (m, 2H), 6.88 (m, 1H), 5.06 (m, 1H), 2.66 (s, 1H);ESIMS m/z 212 ([M]⁺).

1-(4-Chlorophenyl)-2,2,2-trifluoroethanol (C4)

The product was isolated as a colorless oil (5.0 g, 99%): ¹H NMR (400MHz, CDCl₃) δ 7.44-7.38 (m, 4H), 5.05 (m, 1H), 2.55 (s, 1H); ESIMS m/z210 ([M]⁺).

2,2,2-Trifluoro-1-(4-methoxyphenyl)ethanol (C5)

The product was isolated as a pale yellow liquid: ¹H NMR (400 MHz,CDCl₃) δ 7.41 (d, J=8.8 Hz, 2H), 6.95 (m, J=8.8 Hz, 2H), 5.00 (m, 1H),3.82 (s, 3H), 2.44 (s, 1H); ESIMS m/z 206 ([M]⁺).

2,2,2-Trifluoro-1-(4-fluorophenyl)ethanol (C6)

The product was isolated as a colorless oil (5 g, 99%): ¹H NMR (400 MHz,CDCl₃) δ 7.48-7.45 (m, 2H), 7.13-7.07 (m, 2H), 5.06 (m, 1H), 2.53 (s,1H); ESIMS m/z 194 ([M]⁺).

2,2,2-Trifluoro-1-(p-tolyl)ethanol (C7)

The product was isolated as colorless oil (5.0 g, 99%): ¹H NMR (400 MHz,CDCl₃) δ 7.37 (d, J=8.0 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 5.02 (m, 1H),2.46 (m, 1H), 2.37 (s, 3H); ESIMS m/z 190 ([M]⁺).

2,2,2-Trifluoro-1-(3-fluorophenyl)ethanol (C8)

The product was isolated as a colorless viscous oil (2.8 g, 93%): ¹H NMR(400 MHz, CDCl₃) δ 7.41 (m, 1H), 7.25 (m, 2H), 7.14 (m, 1H), 5.06 (m,1H), 2.60 (s, 1H); ESIMS m/z 194 ([M]⁺).

2,2,2-Trifluoro-1-(2-fluorophenyl)ethanol (C9)

The product was isolated as a colorless oil (2.5 g, 99%): ¹H NMR (400MHz, CDCl₃) δ 7.40 (m, 1H), 7.43 (m, 1H), 7.24 (m, 1H), 7.13 (m, 1H),5.42 (m, 1H), 2.65 (s, 1H); ESIMS m/z 194 ([M]⁺).

The following compounds were made in accordance with the proceduresdisclosed in Step 1 Method B of Example 1.

2,2,2-Trifluoro-1-(3,4,5-trichlorophenyl)ethanol (C10)

The product was isolated as a pale yellow liquid (0.500 g, 65%): ¹H NMR(400 MHz, CDCl₃) δ 7.45 (s, 2H), 5.00 (m, 1H), 2.80 (s, 1H); ESIMS m/z278 ([M+H]⁺); IR (thin film) 3420, 1133, 718 cm⁻¹.

1-(3,5-Dichloro-4-fluorophenyl)-2,2,2-trifluoroethanol (C11)

The product was isolated as a pale yellow liquid (0.500 g, 65%): ¹H NMR(400 MHz, CDCl₃) δ 7.41 (s, 2H), 5.00 (m, 1H), 2.80 (s, 1H); ESIMS m/z262 ([M+H]⁺); IR (thin film) 3420, 1133, 718 cm⁻¹.

1-(3,4-Dichlorophenyl)-2,2,2-trifluoroethanol (C12)

The product was isolated as a pale yellow liquid (0.500 g, 65%): ¹H NMR(400 MHz, CDCl₃) δ 7.60 (s, 1H), 7.51 (m, 1H), 7.35 (m, 1H), 5.01 (m,1H), 2.60 (s, 1H); EIMS m/z 244 ([M]⁺).

1-(3-Chlorophenyl)-2,2,2-trifluoroethanol (C13)

The product was isolated as a colorless viscous oil (1.5 g, 75%): ¹H NMR(400 MHz, CDCl₃) δ 7.50 (s, 1H), 7.42-7.35 (m, 3H), 5.02 (m, 1H), 2.65(br s, 1H).

2,2,2-Trifluoro-1-phenylethanol (C14)

The product was isolated (10 g, 80%): ¹H NMR (300 MHz, CDCl₃) δ 7.48 (m,2H), 7.40 (m, 3H), 5.02 (m, 1H), 2.65 (d, J=7.1 Hz, 1H).

1-(3,5-Dimethylphenyl)-2,2,2-trifluoroethanol (C15)

The product was isolated as an off white solid: 1H NMR (400 MHz, CDCl₃)δ 7.05 (s, 2H), 7.02 (s, 1H), 4.95 (m, 1H), 2.32 (s, 6H); ESIMS m/z 204([M]⁻).

1-(2,4-Dichlorophenyl)-2,2,2-trifluoroethanol (C16)

The product was isolated as an off white powder (5.3 g, 61%): mp 49-51°C.; ¹H NMR (400 MHz, CDCl₃) δ 7.62-7.66 (d, 1H), 7.42-7.44 (d, 1H),7.32-7.36 (d, 1H), 5.6 (m, 1H), 2.7 (s, 1H); ESIMS m/z 244 ([M]⁺).

1-(2,3-Dichlorophenyl)-2,2,2-trifluoroethanol (C17)

The product was isolated as a pale yellow oil (5.2 g, 60%): ¹H NMR (400MHz, CDCl₃) δ 7.62-7.64 (d, 1H), 7.52-7.54 (m, 1H), 7.29-7.33 (t, 1H),5.6-5.76 (m, 1H), 2.7 (s, 1H); ESIMS m/z 244 ([M]⁺).

1-(2,5-Dichlorophenyl)-2,2,2-trifluoroethanol (C19)

The product was isolated as a yellow oil (4.1 g, 60%): ¹H NMR (400 MHz,CDCl₃) δ 7.68-7.7 (s, 1H), 7.3-7.37 (m, 2H), 5.51-5.6 (m, 1H), 2.7 (s,1H); ESIMS m/z 244 ([M]⁺).

1-(3,5-Bis(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol (C20)

The product was isolated (3.8 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.98(m, 3H), 5.25 (m, 1H), 3.2 (br, 1H); ESIMS m/z 312 ([M]⁺).

2,2,2-Trifluoro-1-(2,3,5-trichlorophenyl)ethanol (C21)

The product was isolated as a white solid (4.0 g, 60%): mp 113-115° C.;¹H NMR (400 MHz, CDCl₃) δ 7.62 (d, 1H), 7.50 (d, 1H), 5.60-5.70 (m, 1H),2.75 (s, 1H); ESIMS m/z 278 ([M⁺]).

1-(3-Chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol (C22)

The product was isolated as a pale yellow oil (2.0 g, 50%): ¹H NMR (400MHz, CDCl₃) δ 7.51 (m, 3H), 5.08 (m, 1H), 2.81 (s, 1H); ESIMS m/z 278([M]⁺).

1-(3,5-Dichloro-4-methoxyphenyl)-2,2,2-trifluoroethanol (C23)

The product was isolated as an off white solid (0.8 g, 60%); mp 92-95°C.: ¹H NMR (400 MHz, CDCl₃) δ 7.41 (s, 2H), 5.00 (m, 1H), 3.89 (s, 3H),2.64 (m, 1H); ESIMS m/z 274 ([M]⁺).

The following compounds were made in accordance with the proceduresdisclosed in Step 1 Method B of Example 1 above.

1-(3,5-Dibromophenyl)-2,2,2-trifluoroethanol (C24)

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz,CDCl₃) δ 7.67 (s, 1H), 7.58 (s, 2H), 5.08-5.02 (m, 1H), 4.42 (bs, 1H);EIMS m/z 333.7 ([M]⁺); IR (thin film) 3417, 2966, 1128, 531 cm⁻¹.

1-(4-Bromo-3,5-dichlorophenyl)-2,2,2-trifluoroethanol (C25)

The product was isolated as a colorless liquid: ¹H NMR (300 MHz,DMSO-d₆) δ 7.75 (s, 2H), 7.24 (d, J=6.0 Hz, 1H), 5.34-5.29 (m, 1H); EIMSm/z 321.88 ([M]⁺); IR (thin film) 3420, 1706, 1267, 804, 679 cm⁻¹.

1-(3,5-Dibromo-4-chlorophenyl)-2,2,2-trifluoroethanol (C26)

The product was isolated as a pale yellow gum: ¹H NMR (300 MHz, DMSO-d₆)δ 7.89 (s, 2H), 7.20 (d, J=6.0 Hz, 1H) 5.34-5.30 (m, 1H); EIMS m/z 366.0([M]⁺).

The following compounds were made in accordance with the proceduresdisclosed in Step 2 of Example 1.

5-(1-Bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (C27)

The product was isolated as a colorless oil (0.300 g, 60%): ¹H NMR (400MHz, CDCl₃) δ 7.59 (s, 2H), 5.00 (m, 1H); EIMS m/z 340 ([M]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (C28)

The product was isolated as a colorless oil (0.320 g, 60%): ¹H NMR (400MHz, CDCl₃) δ 7.45 (s, 2H), 5.00 (m, 1H); EIMS m/z 324 ([M]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-1,2-dichlorobenzene (C29)

The product was isolated as a colorless oil (0.300 g, 60%): ¹H NMR (400MHz, CDCl₃) δ 7.63 (s, 1H), 7.51 (m, 1H), 7.35 (m, 1H), 5.01 (m, 1H);EIMS m/z 306 ([M]⁺).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-chlorobenzene (C30)

The product was isolated (0.14 g, 22%): ¹H NMR (400 MHz, CDCl₃) δ 7.50(br s, 1H), 7.42-7.35 (m, 3H), 5.07 (m, 1H).

(1-Bromo-2,2,2-trifluoroethyl)benzene (C31)

The product was isolated as a liquid (8.0 g, 60%): ¹H NMR (400 MHz,CDCl₃) δ 7.50 (m, 2H), 7.40 (m, 3H), 5.00 (q, J=7.5 Hz, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dimethylbenzene (C32)

The product was isolated and carried on crude (3.0 g, 51%).

1-(1-Bromo-2,2,2-trifluoroethyl)-2,4-dichlorobenzene (C33)

The product was isolated (3.2 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ7.62-7.72 (m, 1H), 7.4-7.42 (m, 1H), 7.3-7.38 (m, 1H), 5.7-5.8 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-2,3-dichlorobenzene (C34)

The product was isolated as an oil (8.7 g, 60%): ¹H NMR (400 MHz, CDCl₃)δ 7.62-7.71 (m, 1H), 7.44-7.52 (m, 1H), 7.27-7.3 (s, 1H), 5.81-5.91 (m,1H).

2-(1-Bromo-2,2,2-trifluoroethyl)-1,4-dichlorobenzene (C35)

The product was isolated (3.0 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ7.7-7.78 (m, 1H), 7.3-7.4 (m, 2H), 5.7-5.8 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-bis(trifluoromethyl)benzene (C36)

The product was prepared and carried on crude.

1-(1-Bromo-2,2,2-trifluoroethyl)-2,3,5-trichlorobenzene (C37)

The product was isolated (2.9 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.70(d, 1H), 7.50 (d, 1H), 5.72-5.82 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-(trifluoromethyl)benzene(C38)

The product was isolated as an oil (2.0 g, 40%): ESIMS m/z 342 ([M]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-methoxybenzene (C39)

The product was isolated as a colorless liquid (0.6 g, 57%).

1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-difluorobenzene (C40)

The product was isolated (3.2 g, 50%); ¹H NMR (400 MHz, CDCl₃) δ 7.05(m, 2H), 6.86 (m, 1H), 5.03 (q, J=7.4 Hz, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-4-chlorobenzene (C41)

The product was isolated (3.0 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.45(d, J=8.2 Hz, 2H), 7.37 (d, J=8.2 Hz, 2H), 5.10 (q, J=7.2 Hz, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-4-methoxybenzene (C42)

The product was isolated (3.8 g, 62%).

1-(1-Bromo-2,2,2-trifluoroethyl)-4-fluorobenzene (C43)

The product was prepared and carried on as crude intermediate.

1-(1-Bromo-2,2,2-trifluoroethyl)-4-methylbenzene (C44)

The product was isolated (3.0 g, 45%).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-fluorobenzene (C45)

The product was isolated (2.0 g, 61%).

1-(1-Bromo-2,2,2-trifluoroethyl)-2-fluorobenzene (C46)

The product was isolated (2.0 g, 61%): ¹H NMR (400 MHz, CDCl₃) δ 7.61(m, 1H), 7.40 (m, 1H), 7.23 (m, 1H), 7.10 (m, 1H), 5.40 (m, 1H); GCMSm/z 255 ([M]⁺).

1,3-Dibromo-5-(1-bromo-2,2,2-trifluoroethyl)benzene (C47)

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz,CDCl₃) δ 7.71 (s, 1H), 7.59 (s, 2H), 5.04-4.97 (m, 1H); EIMS m/z 394.6([M]⁺); IR (thin film) 1114, 535 cm⁻¹.

2-Bromo-5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichlorobenzene (C48)

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz,DMSO-d₆) δ 7.79 (s, 2H), 6.27-6.21 (m, 1H); EIMS m/z 383.9 ([M]⁺); IR(thin film) 2924, 1114, 749, 534 cm⁻¹.

1,3-Dibromo-5-(1-bromo-2,2,2-trifluoroethyl)-2-chlorobenzene (C49)

The title molecule was isolated as a pale yellow liquid: ¹H NMR (300MHz, DMSO-d₆) δ 7.97 (s, 2H), 6.27-6.19 (m, 1H); EIMS m/z 428.0 ([M]⁺).

Example 3: Preparation of ethyl 2-methyl-4-vinylbenzoate (C52)

Step 1. 4-Formyl-2-methylbenzoic acid (C50)

To a stirred solution of 4-bromo-2-methylbenzoic acid (10.0 g, 46.4mmol) in dry tetrahydrofuran (360 mL) at −78° C. was addedn-butyllithium (1.6 M solution in hexane, 58.2 mL, 93.0 mmol) anddimethylformamide (8 mL). The reaction mixture was stirred at −78° C.for 1 hour then was warmed to 25° C. and stirred for 1 hour. Thereaction mixture was quenched with hydrochloric acid (1 N) and extractedwith ethyl acetate. The combined ethyl acetate extracts were washed withbrine, dried over sodium sulfate, and concentrated under reducedpressure. The residue was washed with n-hexane to afford the titlecompound as a solid (3.00 g, 40%): mp 196-198° C.; ¹H NMR (400 MHz,DMSO-d₆) δ 13.32 (br s, 1H), 10.05 (s, 1H), 7.98 (m, 1H), 7.84 (m, 2H),2.61 (s, 3H); ESIMS m/z 163 ([M−H]⁻).

Step 2. Ethyl 4-formyl-2-methylbenzoate (C51)

To a stirred solution of 4-formyl-2-methylbenzoic acid (C50) (3.00 g,18.2 mmol) in ethyl alcohol (30 mL) was added sulfuric acid (2 mL), andthe reaction mixture was heated at 80° C. for 18 hours. The reactionmixture was cooled to 25° C. and concentrated under reduced pressure.The residue was diluted with ethyl acetate and washed with water. Thecombined ethyl acetate extracts were washed with brine, dried oversodium sulfate and concentrated under reduced pressure to afford thetitle compound as a solid (2.80 g, 80%): ¹H NMR (400 MHz, CDCl₃) δ 10.05(s, 1H), 8.04 (m, 1H), 7.75 (m, 2H), 4.43 (m, 2H), 2.65 (s, 3H), 1.42(m, 3H).

Step 3. Ethyl 2-methyl-4-vinylbenzoate (C52)

To a stirred solution of ethyl 4-formyl-2-methylbenzoate (C51) (2.8 g,4.0 mmol) in 1,4-dioxane (20 mL) were added potassium carbonate (3.0 g,22 mmol) and methyltriphenyl phosphonium bromide (7.8 g, 22 mmol) at 25°C. Then the reaction mixture was heated at 100° C. for 18 hours. Afterthe reaction was deemed complete by thin layer chromatography, thereaction mixture was cooled to 25° C. and filtered, and the filtrate wasconcentrated under reduced pressure. The crude compound was purified byflash column chromatography using 25-30% ethyl acetate/hexanes as eluentto afford the title compound as a solid (2.0 g, 72%): ¹H NMR (400 MHz,CDCl₃) δ 7.86 (m, 1H), 7.27 (m, 2H), 6.68 (dd, J=17.6, 10.8 Hz, 1H),5.84 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz, 1H), 4.39 (m, 2H), 2.60 (s,3H), 1.40 (m, 3H); ESIMS m/z 191 ([M−H]⁻); IR (thin film) 2980, 1716,1257 cm⁻¹.

Example 4: Preparation of tert-butyl 2-chloro-4-vinylbenzoate (C54)

Step 1. tert-Butyl 4-bromo-2-chlorobenzoate (C53)

To a stirred solution of 4-bromo-2-chlorobenzoic acid (5.00 g, 21.4mmol) in tetrahydrofuran (30 mL) was added di-tert-butyl dicarbonate(25.5 g, 25.6 mmol), triethylamine (3.20 g, 32.0 mmol) and4-dimethylaminopyridine (0.780 g, 6.40 mmol), and the reaction mixturewas stirred at 25° C. for 18 hours. The reaction mixture was dilutedwith ethyl acetate and washed with water. The combined organic layer waswashed with brine, dried over sodium sulfate, and concentrated underreduced pressure. The residue was purified by flash columnchromatography using 2-3% ethyl acetate/hexanes as eluent to afford thetitle compound as a liquid (3.20 g, 51%): ¹H NMR (400 MHz, CDCl₃) δ 7.62(m, 2H), 7.44 (d, J=8.4 Hz, 1H), 1.59 (s, 9H); ESIMS m/z 290 ([M+H]⁺);IR(thin film) 1728 cm⁻¹.

Step 2. tert-Butyl 2-chloro-4-vinylbenzoate (C54)

To a stirred solution of tert-butyl 4-bromo-2-chlorobenzoate (C53) (1.6g, 5.5 mmol) in toluene (20 mL) was addedtetrakis(triphenylphospine)palladium(0) (0.31 mg, 0.27 mmol), potassiumcarbonate (2.3 g, 17 mmol) and vinylboronic anhydride pyridine complex(2.0 g, 8.3 mmol) and the reaction mixture was heated to reflux for 16hours. The reaction mixture was filtered, the filtrate was washed withwater and brine, dried over sodium sulfate, and concentrated underreduced pressure. Purification by flash column chromatography using 5-6%ethyl acetate/hexanes as eluent afforded the title compound as a liquid(0.60 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.72 (d, J=8.1 Hz, 1H), 7.44(m, 1H), 7.31 (d, J=8.0 Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.85(d, J=17.6 Hz, 1H), 5.40 (d, J=10.8 Hz, 1H), 1.60 (s, 9H); ESIMS m/z 239([M+H]⁺); IR (thin film) 2931, 1725, 1134 cm⁻¹.

The following compounds were made in accordance with the proceduresdisclosed in Step 1 of Example 4.

tert-Butyl 2-bromo-4-iodobenzoate (C55)

The product was isolated as a colorless oil (1.2 g, 50%): ¹H NMR (400MHz, CDCl₃) δ 8.01 (s, 1H), 7.68 (d, J=8.4 Hz, 1H), 7.41 (d, J=8.0 Hz,1H), 1.59 (s, 9H); ESIMS m/z 382 ([M+H]⁺); IR(thin film) 1727 cm⁻¹.

tert-Butyl 4-bromo-2-(trifluoromethyl)benzoate(C56)

The product was isolated as a colorless oil (1 g, 52%): ¹H NMR (400 MHz,CDCl₃) δ 7.85 (s, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.62 (d, J=8.4 Hz, 1H),1.57 (s, 9H); ESIMS m/z 324 ([M+H]⁺); IR (thin film) 1725 cm⁻¹.

The following compounds were made in accordance with the proceduresdisclosed in Step 2 of Example 4.

tert-Butyl 2-bromo-4-vinylbenzoate (C57)

The product was isolated as a colorless oil (1 g, 52%): ¹H NMR (400 MHz,CDCl₃) δ 7.68 (m, 2H), 7.36 (d, J=8.0 Hz, 1H), 6.68 (dd, J=17.6, 10.8Hz, 1H), 5.84 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz, 1H), 1.60 (s, 9H);ESIMS m/z 282 ([M+H]⁺); IR (thin film) 2978, 1724, 1130 cm⁻¹.

tert-Butyl 2-(trifluoromethyl)-4-vinylbenzoate (C58)

The product was isolated as a colorless oil (1.2 g, 50%): ¹H NMR (400MHz, CDCl₃) δ 7.71 (d, J=6.4 Hz, 2H), 7.59 (d, J=7.6 Hz, 1H), 6.77 (dd,J=17.6, 10.8 Hz, 1H), 5.89 (d, J=17.6 Hz, 1H), 5.44 (d, J=10.8 Hz, 1H),1.58 (s, 9H); ESIMS m/z 272 ([M+H]⁺); IR (thin film) 2982, 1727, 1159cm⁻¹.

Example 5: Preparation of tert-butyl 2-cyano-4-vinylbenzoate (C59)

To a stirred solution of tert-butyl 2-bromo-4-vinylbenzoate (C57) (0.5g, 1.8 mmol) in dimethylformamide (20 mL) was added copper(I) cyanide(0.23 g, 2.7 mmol), and the reaction mixture was heated at 140° C. for 3hours. The reaction mixture was cooled to 25° C., diluted with water,and extracted with ethyl acetate. The combined organic layer was washedwith brine, dried over sodium sulfate, and concentrated under reducedpressure. The residue was purified by flash column chromatography using15% ethyl acetate/hexanes as eluent to afford the title compound as awhite solid (0.30 g, 72%): mp 51-53° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.03(s, 1H), 7.77 (s, 1H), 7.64 (d, J=8.4 Hz, 1H), 6.75 (dd, J=17.6, 10.8Hz, 1H), 5.93 (d, J=17.6 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H), 1.65 (s, 9H);ESIMS m/z 230 ([M+H]⁺); IR (thin film) 2370, 1709, 1142 cm⁻¹.

Example 6: Preparation of ethyl 2-bromo-4-iodobenzoate (C60)

To a stirred solution of 4-iodo-2-bromobenzoic acid (5.00 g, 15.3 mmol)in ethyl alcohol (100 mL) was added sulfuric acid (5 mL), and thereaction mixture was heated at 80° C. for 18 hours. The reaction mixturewas cooled to 25° C. and concentrated under reduced pressure. Theresidue was diluted with ethyl acetate (2×100 mL) and washed with water(100 mL). The combined ethyl acetate extracts were washed with brine,dried over sodium sulfate, and concentrated under reduced pressure toafford the compound as a pale yellow solid (5.00 g, 92%): ¹H NMR (400MHz, DMSO-d₆) δ 8.04 (d, J=1.2 Hz, 1H), 7.71 (d, J=7.6 Hz, 1H), 7.51 (d,J=8.4 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.41 (t, J=7.2 Hz, 3H).

The following compounds were made in accordance with the proceduresdisclosed in Example 6.

Ethyl 4-bromo-2-chlorobenzoate (C61)

The title compound was isolated as an off-white solid (2.0 g, 80%): ¹HNMR (400 MHz, DMSO-d₆) δ 8.25 (d, J=1.2 Hz, 1H), 7.79 (d, J=7.6 Hz, 1H),7.65 (d, J=8.4 Hz, 1H), 4.65 (q, J=7.2 Hz, 2H), 1.56 (t, J=7.2 Hz, 3H).

Ethyl 4-bromo-2-methylbenzoate (C62)

The title compound was isolated as a pale yellow liquid (3.0 g, 83%): ¹HNMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.4 Hz, 1H), 7.41 (s, 1H), 7.39 (d,J=8.4 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 2.60 (s, 3H), 1.40 (t, J=7.2 Hz,3H); ESIMS m/z 229 ([M+H]⁺); IR (thin film) 1725 cm⁻¹.

Ethyl 4-bromo-2-fluorolbenzoate (C63)

The title compound was isolated as a colorless liquid (9.0 g, 79%): ¹HNMR (400 MHz, DMSO-d₆) δ 7.84 (t, J=8.4 Hz, 1H), 7.76 (d, J=2.0 Hz, 1H),7.58 (d, J=1.6 Hz, 1H), 4.34 (q, J=7.2 Hz, 2H), 1.32 (t, J=7.2 Hz, 3H);ESIMS m/z 247 ([M+H]*), IR (thin film) 1734 cm⁻¹.

Example 7: Preparation of ethyl 4-bromo-2-ethylbenzoate (C64)

To a stirred solution of 4-bromo-2-fluorobenzoic acid (2.0 g, 9.2 mmol)in tetrahydrofuran (16 mL), was added ethyl magnesium bromide (1.0 M intetrahydrofuran, 32 mL, 32.0 mmol) dropwise at 0° C. and the resultantreaction mixture was stirred at ambient temperature for 18 hours. Thereaction mixture was quenched with hydrochloric acid (2 N) and extractedwith ethyl acetate. The combined ethyl acetate layer was dried overanhydrous sodium sulfate and concentrated under reduced pressure toafford crude 4-bromo-2-ethylbenzoic acid as a colorless liquid that wasused in the next step without purification (0.40 g): ¹H NMR (400 MHz,CDCl₃) δ 7.64 (d, J=8.4 Hz, 1H), 7.47 (m, 1H), 7.43 (m, 1H), 2.95 (q,J=4.0 Hz, 2H), 1.32 (t, J=4.0 Hz, 3H); ESIMS m/z 229 ([M+H]⁺).

Alternatively, the title compound was synthesized from4-bromo-2-ethylbenzoic acid in accordance to the procedure in Example 6and isolated as a colorless liquid (0.15 g, 68%): ¹H NMR (400 MHz,DMSO-d₆) δ 7.90 (d, J=8.4 Hz, 1H), 7.47 (m, 2H), 4.40 (q, J=7.2 Hz, 2H),3.06 (q, J=7.6 Hz, 2H), 1.42 (t, J=7.2 Hz, 3H), 1.26 (t, J=7.6 Hz, 3H);ESIMS m/z 227 ([M−H]⁻); IR (thin film) 3443, 1686, 568 cm⁻¹.

Example 8: Preparation of ethyl 2-bromo-4-vinylbenzoate (C65)

To a stirred solution of ethyl 2-bromo-4-iodobenzoate (C60) (5.00 g,14.3 mmol) in tetrahydrofuran/water (100 mL, 9:1) was added potassiumvinyltrifluoroborate (1.89 g, 14.3 mmol), cesium carbonate (18.3 g, 56.1mmol), and triphenylphosphine (0.220 g, 0.850 mmol). The reactionmixture was degassed with argon for 20 minutes, then charged withdichloropalladium(II) (0.0500 g, 0.280 mmol). The reaction mixture washeated to reflux for 16 hours. The reaction mixture was cooled toambient temperature and filtered through a Celite® bed and washed withethyl acetate. The filtrate was again extracted with ethyl acetate andthe combined organic layers washed with water and brine, dried oversodium sulfate, and concentrated under reduced pressure to afford crudecompound. The crude compound was purified by flash column chromatographyusing 2% ethyl acetate/petroleum ether as eluent to afford the titlecompound as a light brown gummy material (2.00 g, 56%): ¹H NMR (400 MHz,CDCl₃) δ 7.78 (d, J=8.4 Hz, 1H), 7.71 (d, J=1.2 Hz, 1H), 7.51 (d, J=8.4Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.42(d, J=11.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 1.43 (t, J=3.6 Hz, 3H);ESIMS m/z 255 ([M+H]⁺); IR (thin film) 1729 cm⁻¹.

The following compounds were made in accordance with the proceduresdisclosed in Example 8.

Ethyl 2-methyl-4-vinylbenzoate (C66)

The title compound was isolated as a colorless liquid (0.8 g, 80%): ¹HNMR (400 MHz, CDCl₃) δ 7.89 (d, J=8.4 Hz, 1H), 7.27 (m, 2H), 6.79 (dd,J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.42 (d, J=11.2 Hz, 1H),4.42 (q, J=7.2 Hz, 2H), 2.60 (s, 3H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z191 ([M+H]⁺); IR (thin film) 1717, 1257 cm⁻¹.

Ethyl 2-fluoro-4-vinylbenzoate (C67)

The title compound was isolated as a pale yellow liquid (2.0 g, 50%): ¹HNMR (400 MHz, DMSO-d₆) δ 7.87 (t, J=8.0 Hz, 1H), 7.51 (d, J=16.0 Hz,1H), 7.48 (d, J=16.0 Hz, 1H), 6.82 (dd, J=17.6, 10.8 Hz, 1H), 6.09 (d,J=17.6 Hz, 1H), 5.50 (d, J=10.8 Hz, 1H), 4.35 (q, J=7.2 Hz, 2H), 1.35(t, J=7.2 Hz, 3H); ESIMS m/z 195 ([M+H]⁺); IR (thin film) 1728 cm⁻¹.

Example 9: Preparation of ethyl 2-chloro-4-vinylbenzoate (C68)

To a stirred solution of ethyl 2-chloro-4-bromobenzoate (C61) (2.00 g,7.63 mmol) in dimethylsulfoxide (20 mL) was added potassiumvinyltrifluoroborate (3.06 g, 22.9 mmol), and potassium carbonate (3.16g, 22.9 mmol). The reaction mixture was degassed with argon for 30minutes. Bistriphenylphosphine(diphenylphosphino ferrocene)palladium(II)dichloride (0.270 g, 0.380 mmol) was added and the reaction mixture washeated to 80° C. for 1 hour. The reaction mixture was diluted with water(100 mL), extracted with ethyl acetate (2×50 mL), washed with brine,dried over sodium sulfate, and concentrated under reduced pressure toobtain the compound as brown gummy material (1.10 g, 69%): ¹H NMR (400MHz, CDCl₃) δ 7.81 (d, J=8.4 Hz, 1H), 7.46 (s, 1H), 7.33 (d, J=8.4 Hz,1H), 6.70 (dd, J=17.6, 11.2 Hz, 1H), 5.87 (d, J=17.6 Hz, 1H), 5.42 (d,J=10.8 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.43 (t, J=7.2 Hz, 3H); ESIMSm/z 211 ([M+H]⁺); IR (thin film) 1729, 886 cm⁻¹.

The following compounds were made in accordance with the proceduresdisclosed in Example 9.

Ethyl 2-ethyl-4-vinylbenzoate (C69)

The title compound was isolated as a colorless liquid (1.0 g, 66%): ¹HNMR (300 MHz, CDCl₃) δ 7.85 (m, 1H), 7.29 (m, 2H), 6.76 (d, J=10.8 Hz,1H), 5.86 (d, J=17.6 Hz, 1H), 5.36 (d, J=10.5 Hz, 1H), 4.41 (q, J=7.2Hz, 2H), 3.10 (q, J=7.2 Hz, 2H), 1.40 (t, J=7.2 Hz, 3H), 1.30 (t, J=7.2Hz, 3H); ESIMS m/z 205 ([M+H]⁺); IR (thin film) 1720, 1607, 1263 cm⁻¹.

Methyl 2-methoxy-4-vinylbenzoate (C70)

The title compound was isolated as a pale yellow liquid (1.2 g, 75%): ¹HNMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.04 (d, J=1.2 Hz, 1H),6.97 (s, 1H), 6.74 (dd, J=11.2, 11.2 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H),5.39 (d, J=17.6 Hz, 1H) 3.93 (s, 3H), 3.91 (s, 3H); ESIMS m/z 193([M+H]⁺); IR (thin film) 1732 cm⁻¹,

Example 10: Preparation of (E)-ethyl4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate(C71)

To a stirred solution of ethyl 2-methyl-4-vinylbenzoate (C66) (2.00 g,10.5 mmol) in 1,2-dichlorobenzene (25 mL) were added1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (C2) (6.44 g, 21.0mmol), copper(I) chloride (0.208 g, 21.0 mmol) and 2,2′-bipyridyl (0.650g, 4.10 mmol). The reaction mixture was degassed with argon for 30minutes and then stirred at 180° C. for 24 hours. After the reaction wasdeemed complete by thin layer chromatography, the reaction mixture wascooled to 25° C. and filtered, and the filtrate was concentrated underreduced pressure. Purification by flash column chromatography using25-30% ethyl acetate/petroleum ether as eluent afforded the titlecompound as a solid (1.70 g, 40%): ¹H NMR (400 MHz, CDCl₃) δ 7.91 (d,J=8.0 Hz, 1H), 7.37 (m, 1H), 7.27-7.24 (m, 4H), 6.59 (d, J=16.0 Hz, 1H),6.59 (dd, J=16.0, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 4.08 (m, 1H),2.62 (s, 3H), 1.42 (t, J=7.2 Hz, 3H); ESIMS m/z 415 ([M−H]⁻); IR (thinfilm) 1717, 1255, 1114 cm⁻¹.

The following compounds were made in accordance with the proceduresdisclosed in Example 10.

(E)-Ethyl4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)-benzoate(C72)

The product was isolated as a pale brown gummy liquid (0.500 g, 40%): ¹HNMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1), 7.71 (m, 1H), 7.61 (d,J=7.6 Hz, 1H), 7.42 (s, 2H), 6.70 (d, J=16.0 Hz, 1H), 6.57 (dd, J=16.0,8.0 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 4.19 (m, 1H), 1.40 (t, J=7.6 Hz,3H); ESIMS m/z 503 ([M−H]⁻); IR (thin film) 1730, 1201, 1120, 749 cm⁻¹.

(E)-Ethyl4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluorobenzoate(C73)

¹H NMR (400 MHz, CDCl₃) δ 7.38 (s, 1H), 7.26 (s, 3H), 7.21 (d, J=8.4 Hz,1H), 7.16 (d, J=11.6 Hz, 1H), 6.59 (d, J=16.0 Hz, 1H), 6.47 (dd, J=16.0,8.0 Hz, 1H), 4.41 (q, J=6.8 Hz, 2H), 4.18 (m, 1H), 1.41 (t, J=6.8 Hz,3H); ESIMS m/z 419 ([M−H]⁻); IR (thin film) 1723, 1115, 802 cm⁻¹.

(E)-Ethyl4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-bromobenzoate(C74)

¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.67 (s, 1H), 7.38 (m,2H), 7.26 (m, 2H), 6.56 (d, J=16.0 Hz, 1H), 6.45 (dd, J=16.0, 7.6 Hz,1H), 4.42 (q, J=7.2 Hz, 2H), 4.39 (m, 1H), 1.42 (t, J=7.2 Hz, 3H); ESIMSm/z 481 ([M−H]⁻); IR (thin film) 1727, 1114, 801, 685 cm⁻¹.

(E)-Ethyl 2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoate (C75)

¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.67 (d, J=1.6 Hz,1H), 7.40 (s, 2H), 7.36 (d, J=1.6 Hz, 1H), 6.56 (d, J=16.0 Hz, 1H), 6.44(dd, J=16.0, 7.6 Hz, 1H), 4.42 (q, J=6.8 Hz, 2H), 4.15 (m, 1H), 1.42 (t,J=6.8 Hz, 3H); ESIMS m/z 515 ([M−H]⁻); IR (thin film) 1726, 1115, 808,620 cm⁻¹.

(E)-Ethyl 2-methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoate (C76)

The title compound was isolated as a light brown gummy material: ¹H NMR(400 MHz, CDCl₃) δ 7.90 (d, J=8.8 Hz, 1H), 7.34 (d, J=6.0 Hz, 2H), 7.25(d, J=7.2 Hz, 2H), 6.59 (d, J=16.0 Hz, 1H), 6.42 (dd, J=16.0, 8.0 Hz,1H), 4.38 (q, J=7.2 Hz, 2H), 4.19 (m, 1H), 2.63 (s, 3H), 1.41 (t, J=7.2Hz, 3H).

(E)-Ethyl 2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoate (C77)

¹H NMR (400 MHz, CDCl₃) δ 7.87 (d, J=8.0 Hz, 1H), 7.46 (d, J=1.6 Hz,1H), 7.40 (s, 2H), 7.31 (d, J=1.6 Hz, 1H), 6.57 (d, J=16.0 Hz, 1H), 6.44(dd, J=16.0 Hz, 8.0 Hz, 1H), 4.42 (q, J=6.8 Hz, 2H), 4.15 (m, 1H), 1.42(t, J=6.8 Hz, 3H); ESIMS m/z 471 ([M−H]⁻); IR (thin film) 1726, 1115,809, 3072 cm⁻¹.

(E)-Ethyl4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzoate(C78)

The title compound was isolated as a pale brown liquid (1.0 g, 46.3%):¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.71 (s, 1H), 7.61 (d,J=7.6 Hz, 1H), 7.41 (s, 2H) 6.65 (d, J=16.0 Hz, 1H), 6.49 (dd, J=16.0,8.0 Hz, 1H), 4.42 (q, J=7.6 Hz, 2H), 4.15 (m, 1H), 1.42 (t, J=7.6 Hz,3H); ESIMS m/z 503 ([M−H]⁻); IR (thin film) 1730, 1202, 1120, 750 cm⁻¹.

(E)-Ethyl2-chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate(C79)

¹H NMR (400 MHz, CDCl₃) δ 7.85 (d, J=6.0 Hz, 1H), 7.46 (d, J=1.8 Hz,2H), 7.34 (m, 1H), 7.24 (m, 1H), 6.57 (d, J=16.2 Hz, 1H), 6.45 (dd,J=16.2, 7.2 Hz, 1H), 4.43 (q, J=7.2 Hz, 2H), 4.13 (m, 1H), 1.41 (t,J=7.2 Hz, 3H); ESIMS m/z 455 ([M+H]⁺); IR (thin film) 1728, 1115, 817cm⁻¹.

(E)-Ethyl2-fluoro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate(C80)

¹H NMR (400 MHz, CDCl₃) δ 7.93 (t, J=7.6 Hz, 1H), 7.34 (d, J=5.6 Hz,2H), 7.21 (d, J=8.0 Hz, 1H), 7.16 (d, J=11.6 Hz, 1H), 6.59 (d, J=16.0Hz, 1H), 6.49 (dd, J=16.0, 7.6 Hz, 1H), 4.42 (q, J=7.6 Hz, 2H), 4.13 (m,1H), 1.41 (t, J=7.6 Hz, 3H); ESIMS m/z 436.81([M−H]⁻); IR (thin film)1725 cm⁻¹.

(E)-Ethyl2-bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate(C81)

¹H NMR (400 MHz, CDCl₃) δ 7.94 (d, J=8.0 Hz, 1H), 7.67 (s, 1H), 7.36 (m,3H), 6.56 (d, J=15.6 Hz, 1H), 6.44 (dd, J=15.6, 8.0 Hz, 1H), 4.42 (q,J=6.8 Hz, 2H), 4.10 (m, 1H), 1.42 (t, J=6.8 Hz, 3H); ESIMS m/z 499([M−H]⁻); IR (thin film) 1726, 1114, 820, 623 cm⁻¹.

(E)-Ethyl2-methyl-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate(C82)

The title compound was isolated as a brown semi-solid: ¹H NMR (400 MHz,CDCl₃) δ 7.90 (d, J=8.8 Hz, 1H), 7.34 (d, J=6.0 Hz, 2H), 7.25 (d, J=7.2Hz, 2H), 6.59 (d, J=16.0 Hz, 1H), 6.42 (dd, J=16.0 Hz, 8.0 Hz, 1H), 4.38(q, J=7.2 Hz, 2H), 4.19 (m, 1H), 2.63 (s, 3H), 1.41 (t, J=7.2 Hz, 3H);ESIMS m/z 433 ([M−H]⁻); IR (thin film) 1715 cm⁻¹.

(E)-Methyl2-methoxy-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate(C83)

¹H NMR (400 MHz, CDCl₃) δ 7.80 (d, J=8.4 Hz, 1H), 7.35 (d, J=6.0 Hz,2H), 7.03 (d, J=1.2 Hz, 1H), 6.92 (s, 1H), 6.59 (d, J=15.6 Hz, 1H), 6.42(dd, J=15.6, 8.0 Hz, 1H), 4.13 (m, 1H), 3.93 (s, 3H), 3.88 (s, 3H);ESIMS m/z 437 ([M+H]⁺); IR (thin film) 1724 cm⁻¹.

(E)-Ethyl2-ethyl-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate(C84)

¹H NMR (400 MHz, CDCl₃) δ 7.85 (d, J=8.0 Hz, 1H), 7.35 (d, J=9.6 Hz,2H), 7.26 (m, 1H), 7.24 (m, 1H), 6.60 (d, J=15.6 Hz, 1H), 6.42 (dd,J=15.6, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 4.14 (m, 1H), 3.01 (q,J=7.6 Hz 2H), 1.41 (t, J=7.2 Hz, 3H), 1.26 (t, J=7.6 Hz, 3H); ESIMS m/z447 ([M−H]⁻); IR (thin film) 1715, 1115, 817 cm⁻¹.

Example 11: Preparation of(E)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoicacid (C85)

To a stirred solution of (E)-ethyl4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate(C71) (1.7 g, 4.0 mmol) in 1,4-dioxane (10 mL) was added hydrochloricacid (11 N, 30 mL), and the reaction mixture was heated at 100° C. for48 hours. The reaction mixture was cooled to 25° C. and concentratedunder reduced pressure. The residue was diluted with water and extractedwith chloroform. The combined organic layer was dried over sodiumsulfate and concentrated under reduced pressure. The crude compound waswashed with n-hexane to afford the title compound as a white solid (0.70g, 50%): mp 142-143° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 12.62 (br s, 1H),7.81 (d, J=8.0 Hz, 1H), 7.66 (s, 3H), 7.52-7.44 (m, 2H), 6.89 (dd,J=16.0, 8.0 Hz, 1H), 6.78-6.74 (d, J=16.0 Hz, 1H), 4.84 (m, 1H), 2.50(s, 3H); ESIMS m/z 387 ([M−H]⁻); IR (thin film) 3448, 1701, 1109, 777cm⁻¹.

The following compounds were made in accordance with the proceduresdisclosed in Example 11.

(E)-2-Methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoicacid (C86)

The product was isolated as a pale brown gummy liquid (1 g, 46%): ¹H NMR(400 MHz, CDCl₃) δ 7.97 (d, J=8.0 Hz, 1H), 7.77 (s, 1H), 7.65 (m, 1H),7.41 (s, 2H), 6.68 (d, J=16.0 Hz, 1H), 6.53 (dd, J=16.0, 8.0 Hz, 1H),4.16 (m, 1H), 2.50 (s, 3H); ESIMS m/z 423 ([M−H]⁻).

(E)-2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoicacid (C87)

The product was isolated as an off-white semi-solid (1 g, 45%): ¹H NMR(400 MHz, CDCl₃) δ 7.99 (d, J=8.4 Hz, 1H), 7.50 (m, 1H), 7.40 (s, 1H),7.36 (m, 2H), 6.59 (d, J=15.6 Hz, 1H), 6.48 (dd, J=15.6, 7.6 Hz, 1H),4.14 (m, 1H); ESIMS m/z 443 ([M−H]⁻); IR (thin film) 3472, 1704, 1113,808 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoicacid (C88)

The product was isolated as a brown solid (1 g, 45%): mp 70-71° C.; ¹HNMR (400 MHz, CDCl₃) δ 7.99 (d, J=8.0 Hz, 1H), 7.72 (s, 1H), 7.40 (m,3H), 6.58 (d, J=16.0 Hz, 1H), 6.48 (dd, J=16.0, 8.0 Hz, 1H), 4.14 (m,1H); ESIMS m/z 485 ([M−H]⁻); IR (thin film) 3468, 1700 cm⁻¹.

(E)-2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoicacid (C89)

The product was isolated as an off-white solid (0.500 g, 45%): mp100-101° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.90 (s, 1H), 7.85 (d, J=7.6 Hz,1H), 7.72 (d, J=8.0 Hz, 1H), 7.65 (br s, 1H), 7.42 (s, 2H), 6.73 (d,J=16.0 Hz, 1H), 6.58 (dd, J=16.0, 8.0 Hz, 1H), 4.19 (m, 1H); ESIMS m/z432 ([M−H]⁻).

E)-4-(3-(3,4-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoicacid (C90)

The product was isolated as a pale brown liquid (0.500 g, 46%): ¹H NMR(400 MHz, CDCl₃) δ 8.03 (m, 1H), 7.49 (m, 2H), 7.29 (m, 1H), 7.22 (m,2H), 6.73 (d, J=16.0 Hz, 1H), 6.58 (dd, J=16.0, 7.8 Hz, 1H), 4.16 (m,1H), 2.64 (s, 3H); ESIMS m/z 387 ([M−H]⁻); IR (thin film) 3428, 1690,1113, 780 cm⁻¹.

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoicacid (C91)

The product was isolated as a white solid (500 mg, 50%): mp 91-93° C.;¹H NMR (400 MHz, CDCl₃) δ 8.02 (d, J=8.0 Hz, 1H), 7.35 (d, J=5.6 Hz,1H), 7.30 (m, 3H), 6.61 (d, J=16.0 Hz, 1H), 6.48 (dd, J=16.0, 8.0 Hz,1H), 4.13 (m, 1H), 2.65 (s, 3H); ESIMS m/z 407 ([M−H]⁻).

(E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzoicacid (C92)

The product was isolated as a white solid (500 mg, 45%): mp 142-143° C.;¹H NMR (400 MHz, CDCl₃) δ 7.97 (d, J=8.0 Hz, 1H), 7.77 (s, 1H), 7.65 (m,1H), 7.41 (s, 2H), 6.68 (d, J=16.0 Hz, 1H), 6.53 (dd, J=16.0, 8.0 Hz,1H), 4.16 (m, 1H); ESIMS m/z 475 ([M−H]⁻).

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoicacid (C93)

The title compound was isolated as a brown solid (0.8 g, 28%): ¹H NMR(400 MHz, CDCl₃) δ 13.42 (br, 1H), 7.98 (d, J=1.5 Hz, 1H), 7.94 (m, 2H),7.75 (d, J=8.1 Hz, 1H), 7.65 (m, 1H), 7.06 (dd, J=15.9, 9.0 Hz, 1H),6.80 (d, J=15.9 Hz, 1H), 4.91 (m, 1H); ESIMS m/z 485 ([M−H]⁻); IR (thinfilm) 3469, 1700 cm⁻¹.

(E)-2-Bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoicacid (C94)

The title compound was isolated as a yellow liquid (0.3 g, crude): ¹HNMR (300 MHz, CDCl₃) δ 7.79 (d, J=8.1 Hz, 1H), 7.67 (s, 1H), 7.34 (m,3H), 6.56 (d, J=15.9 Hz, 1H), 6.45 (dd, J=15.9, 7.6 Hz, 1H), 4.43 (m,1H); ESIMS m/z 471 ([M−H]⁻).

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-ethylbenzoicacid (C95)

The title compound was isolated as a brown gummy material (0.2 g,crude): ¹H NMR (300 MHz, DMSO-d₆) δ 12.5 (br, 1H), 7.85 (d, J=6.3 Hz,2H), 7.75 (d, J=8.1 Hz, 1H), 7.52 (m, 2H), 6.96 (dd, J=8.7, 8.7 Hz, 1H),6.78 (d, J=15.6 Hz, 1H), 4.80 (m, 1H), 4.06 (q, J=7.2 Hz, 2H), 1.33 (t,J=7.2 Hz, 3H); ESIMS m/z 419 ([M−H]⁻).

(E)-2-Chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoicacid (C96)

The title compound was isolated as a yellow liquid (0.7 g, 95%): ¹H NMR(300 MHz, CDCl₃) δ 7.85 (d, J=6.0 Hz, 1H), 7.46 (d, J=1.8 Hz, 1H), 7.41(s, 3H), 6.57 (d, J=16.0 Hz, 1H), 6.45 (dd, J=16.0, 8.0 Hz, 1H), 4.16(m, 1H); ESIMS m/z 455 ([M+H]⁺); IR (thin film) 1728, 1115, 817 cm⁻¹.

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoicacid (C97)

The title compound was isolated as a light brown gummy material (0.7 g,38%): mp 91-93° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.02 (d, J=8.0 Hz, 1H),7.35 (d, J=5.6 Hz, 1H), 7.30 (m, 3H), 6.10 (d, J=16.0 Hz, 1H), 6.46 (dd,J=16.0, 8.0 Hz, 1H), 4.03 (m, 1H), 2.65 (s, 3H); ESIMS m/z 407 ([M−H]⁻).

(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluorobenzoicacid (C98)

The title compound was isolated as a light brown liquid (0.3 g, crude):ESIMS m/z 393 ([M−H]⁻).

(E)-2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)benzoicacid (C99)

The title compound was isolated as a light brown liquid (0.35 g, crude):ESIMS m/z 452 ([M−H]⁻).

(E)-4-(3-(4-Bromo-3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methylbenzoicacid (CA1)

The title compound was isolated as a dark brown glass (0.900 g, 80%): ¹HNMR (500 MHz, CDCl₃) δ 8.05 (d, J=8.1 Hz, 1H), 7.40 (s, 2H), 7.30 (dd,J=8.2, 1.7 Hz, 1H), 7.28 (d, J=1.6 Hz, 1H), 6.60 (d, J=15.8 Hz, 1H),6.44 (dd, J=15.9, 8.0 Hz, 1H), 4.11 (p, J=8.6 Hz, 1H), 2.66 (s, 3H); ¹⁹FNMR (471 MHz, CDCl₃) δ −68.63 (d, J=8.8 Hz); ESIMS m/z 466 ([M−H]⁻).

(E)-4-(3-(3,5-Dibromo-4-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methylbenzoic acid(CA2)

The title compound was isolated as a yellow glass (0.900 g, 68%): ¹H NMR(500 MHz, CDCl₃) δ 8.05 (d, J=8.1 Hz, 1H), 7.62 (s, 2H), 7.30 (dd,J=8.3, 1.7 Hz, 1H), 7.28 (d, J=1.5 Hz, 1H), 6.60 (d, J=15.8 Hz, 1H),6.43 (dd, J=15.9, 8.0 Hz, 1H), 4.10 (p, J=8.6 Hz, 1H), 2.67 (s, 3H); ¹⁹FNMR (471 MHz, CDCl₃) δ −68.63 (d, J=8.8 Hz); ESIMS m/z 510 ([M−H]⁻).

(E)-4-(3-(3,5-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methylbenzoicacid (CA3)

The title compound was isolated as a red solid (16.2 g, 82%): ¹H NMR(400 MHz, CDCl₃) δ 8.05 (d, J=8.1 Hz, 1H), 7.68 (t, J=1.7 Hz, 1H), 7.47(d, J=1.7 Hz, 2H), 7.33-7.26 (m, 2H), 6.60 (d, J=15.8 Hz, 1H), 6.45 (dd,J=15.9, 8.0 Hz, 1H), 4.10 (p, J=8.7 Hz, 1H), 2.67 (s, 3H); 19F NMR (376MHz, CDCl₃) δ −68.54; ESIMS m/z 477 ([M−H]⁻).

Example 12: Preparation of(E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(trifluoromethoxy)benzoicacid (C101)

Step 1. 2-(Trifluoromethoxy)-4-vinylbenzoic acid (C100)

To a stirred solution of 4-bromo-2-(trifluoromethoxy)benzoic acid (1.00g, 3.67 mmol) in dimethylsulfoxide (20 mL) was added potassiumvinyltrifluoroborate (1.47 g, 11.0 mmol), and potassium carbonate (1.52g, 11.0 mmol). The reaction mixture was degassed with argon for 30minutes. Bistriphenylphosphine(diphenylphosphino ferrocene)palladium(II)dichloride (0.130 g, 0.180 mmol) was added and the reaction mixture washeated to 80° C. for 1 hour. The reaction mixture was diluted with water(100 mL), extracted with ethyl acetate (2×50 mL), washed with brine, anddried over sodium sulfate. Concentration under reduced pressurefurnished the crude compound which was purified by flash columnchromatography to afford the product as pale yellow gummy material(0.400 g, 47%): ¹H NMR (400 MHz, CDCl₃) δ 8.05 (d, J=8.1 Hz, 1H), 7.44(d, J=1.8 Hz, 1H), 7.35 (s, 1H), 6.78 (dd, J=17.4.1, 11.1 Hz, 1H), 5.92(d, J=17.4 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H); ESIMS m/z 233 ([M+H]*).

Step 2.(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(trifluoromethoxy)benzoicacid (C101)

To a stirred solution of 2-(trifluoromethoxy)-4-vinylbenzoic acid (0.356g, 1.53 mmol) in 1N methyl pyrrolidine (5.0 mL) was added1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichloro 4-fluorobenzene (1.0 g,3.07 mmol), copper(I) chloride (CuCl; 0.03 g, 0.307 mmol) and 2,2bipyridyl (0.095 g, 0.614 mmol). The reaction mixture was stirred at150° C. for 1 h. After the reaction was complete by TLC, the reactionmixture was diluted with water (100 mL) and extracted with ethyl acetate(2×50 mL). The combined organic layers were washed with brine, driedover sodium sulfate and concentrated under reduced pressure to obtainthe crude compound which was purified by flash column chromatography toafford the product as pale yellow gummy material (0.3 g, 21%): ¹H NMR(400 MHz, CDCl₃) δ 8.08 (d, J=8.0 Hz, 1H), 7.45 (d, J=1.6 Hz, 1H), 7.35(s, 3H), 6.63 (d, J=16.0 Hz, 1H), 6.50 (dd, J=16.0, 8.0 Hz, 1H), 4.15(m, 1H); ESIMS m/z 474.81 ([M−H]⁻).

The following molecules were made in accordance with the proceduresdisclosed in Step 2 in Example 12.

(E)-4-(3-(3,5-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C102)

The title molecule was isolated as a brown solid: ¹H NMR (300 MHz,DMSO-d₆) δ 13.5 (bs, 1H), 8.03 (s, 1H), 7.95-7.85 (m, 4H), 7.81 (d,J=7.8 Hz, 1H), 7.14 (dd, J=15.6, 9.6 Hz, 1H), 6.90 (d, J=15.9 Hz, 1H),4.86-4.79 (m, 1H); ESIMS m/z 529 ([M−H]*); IR (thin film) 3437, 1707,1153, 555 cm⁻¹.

(E)-4-(3-(3,5-Dibromo-4-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C103)

Isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ, 13.36 (bs, 1H)8.05 (s, 2H), 7.95 (d, J=8.1 Hz, 1H), 7.87-7.67 (m, 2H), 7.14 (dd,J=9.0, 15.6 Hz, 1H), 6.96 (d, J=15.6 Hz, 1H), 4.88-4.82 (m, 1H); ESIMSm/z 565 ([M+H]⁺).

(E)-4-(3-(4-Bromo-3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C104)

Isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.6 (bs, 1H) 8.03(s, 1H), 7.95 (d, J=8.4 Hz, 1H), 7.88 (s, 2H), 7.81 (d, J=8.1 Hz, 1H),7.13 (dd, J=16.2, 7.5 Hz, 1H), 6.91 (d, J=15.9 Hz, 1H), 4.89-4.83 (m,1H); ESIMS m/z 532 ([M+H]⁺).

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C105)

The title molecule was isolated as an off white solid: mp 140-143° C.;¹H NMR (400 MHz, DMSO-d6) δ13.60 (bs, 1H), 8.02 (s, 1H), 7.94-7.90 (m,1H), 7.88-7.86 (m, 2H), 7.81-7.79 (m, 1H), 7.12 (dd, J=15.6, 8.8 Hz,1H), 6.89 (d, J=15.6 Hz, 1H), 4.86-4.81 (m, 2H); ESIMS m/z 459 ([M−H]⁻).

Example 13: Preparation of(E)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoylchloride (C106)

To a round-bottomed flask (500 mL) equipped with a drying tube, amagnetic stir bar, and(E)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzoic acid (C92) (8.70 g, 18.2 mmol) was added dichloromethane (30mL). To this stirred solution oxalyl dichloride (3.12 mL, 36.4 mmol) wasadded and the reaction was left to stir for 65 hours. The solution wasconcentrated under reduced pressure and the resulting red oil wasdiluted with cyclohexane and concentrated under reduced pressure.

The resulting red oil was placed in a 40° C. vacuum oven for 18 hoursprovided the title compound as a red gum (8.28 g, 92%): ¹H NMR (400 MHz,CDCl₃) δ 8.05 (d, J=8.2 Hz, 1H), 7.83-7.75 (m, 1H), 7.70 (dd, J=8.2, 1.7Hz, 1H), 7.42 (s, 2H), 6.67 (d, J=16.0 Hz, 1H), 6.55 (dd, J=15.9, 7.6Hz, 1H), 4.16 (p, J=8.5 Hz, 1H); 19F NMR (376 MHz, CDCl₃) δ −59.59,−68.47; ¹³C NMR (101 MHz, CDCl₃) δ 165.62, 140.39, 135.01, 134.03,133.68 (q, J=1.8 Hz), 133.18 (q, J=1.8 Hz), 132.29, 132.20, 129.63,129.13 (q, J=33.4 Hz), 129.09, 126.32 (q, J=2.4 Hz), 125.67 (q, J=281.4Hz), 125.28 (q, J=5.6 Hz), 122.45 (q, J=274.1 Hz), 52.38 (q, J=28.9 Hz).

Example 14: Preparation ofN—((R)-1-amino-1-oxopropan-2-yl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(C107)

To a vial (30 mL) containing a magnetic stir bar and(E)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoylchloride (C106) (0.980 g, 1.98 mmol) was added 1,2-dichloroethane (7.9mL) to give a brown solution. (R)-2-Aminopropanamide.hydrochloride(0.295 g, 2.37 mmol) and 4-methylmorpholine (0.652 mL, 5.93 mmol) wereadded and the vial was capped and left to stir overnight. The reactionwas diluted with ethyl acetate (100 mL) and citric acid (5%, 100 mL).The layers were separated and the organic layer was washed with anadditional citric acid (5%, 100 mL), water (100 mL), saturated aqueoussodium bicarbonate (100 mL), and brine (20 mL). The organic phase wasdried with sodium sulfate, filtered, and concentrated to give ared/brown oil. The oil was purified by flash column chromatography using0-100% ethyl acetate/hexanes as eluent. The title compound was isolatedas a beige solid (0.479 g, 44%): ¹H NMR (400 MHz, CDCl₃) δ 7.68 (s, 1H),7.58 (dd, J=8.0, 1.7 Hz, 1H), 7.51 (d, J=8.0 Hz, 1H), 7.42 (s, 2H), 6.73(d, J=7.4 Hz, 1H), 6.62 (d, J=15.9 Hz, 1H), 6.52 (s, 1H), 6.44 (dd,J=15.9, 7.8 Hz, 1H), 5.64 (s, 1H), 4.78 (p, J=7.1 Hz, 1H), 4.21 (m, 1H),1.50 (d, J=6.9 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −59.02, −68.56; ESIMSm/z 549 ([M+H]⁺).

Example 15: Preparation of(E)-N-(2-amino-2-oxoethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(C108)

Into a vial (30 mL) equipped with a magnetic stir bar was added2-aminoacetamide.hydrochloride (0.555 g, 5.02 mmol),(E)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C106) (2.00 g, 4.19 mmol),(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbeniumhexafluorophosphate (2.15 g, 5.02 mmol) and 1,2-dichloroethane (15 mL).4-Methylmorpholine (1.38 mL, 12.6 mmol) was added to this brown solutionand the reaction was capped and left to stir overnight. The reaction wasdiluted with ethyl acetate (150 mL) and (100 mL). The layers wereseparated and the organic layer was washed with an additionalhydrochloric acid (1 M, 100 mL), water (100 mL), saturated aqueoussodium bicarbonate (100 mL), and brine (20 mL). The organic phase wasdried with magnesium sulfate, filtered, and concentrated to give ared/brown oil. The oil was purified by flash column chromatography using0-100% ethyl acetate/hexanes. The title compound was isolated as a beigesolid (1.62, 72%): ¹H NMR (400 MHz, CDCl₃) δ 7.72-7.67 (m, 1H), 7.61(dd, J=8.0, 1.7 Hz, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.42 (s, 2H), 6.71 (t,J=5.1 Hz, 1H), 6.63 (d, J=15.9 Hz, 1H), 6.45 (dd, J=15.9, 7.8 Hz, 1H),6.24 (s, 1H), 5.56 (s, 1H), 4.19 (d, J=5.0 Hz, 2H), 4.16-4.08 (m, 1H);¹⁹F NMR (376 MHz, CDCl₃) 5-59.15, −68.56; ESIMS m/z 535 ([M+H]⁺).

The following compound was prepared in accordance to the procedure inExample 15.

N—((R)-1-Amino-1-oxobutan-2-yl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(C109)

The title compound was prepared with (R)-2-aminobutanamide.hydrochloride in place of 2-aminoacetamide.hydrochloride (2.87, 71%): ¹HNMR (400 MHz, CDCl₃) δ 7.70-7.65 (m, 1H), 7.57 (dd, J=8.0, 1.7 Hz, 1H),7.50 (d, J=8.0 Hz, 1H), 7.42 (s, 2H), 6.74 (dd, J=7.8, 1.4 Hz, 1H), 6.62(d, J=15.9 Hz, 1H), 6.57-6.49 (m, 1H), 6.44 (dd, J=15.9, 7.8 Hz, 1H),5.72 (s, 1H), 4.71 (dt, J=7.7, 6.3 Hz, 1H), 4.19-4.05 (m, 1H), 1.99(ddd, J=13.7, 7.4, 6.1 Hz, 1H), 1.85-1.70 (m, 1H), 1.01 (t, J=7.4 Hz,3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −59.11, −68.57; ESIMS m/z 561 ([M−H]⁻).

Example 16: Preparation ofN—((R)-1-aminoethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide.hydrochloride(C110)

To a vial (5 mL) wrapped in aluminium foil containing a magnetic stirvane andN—((R)-1-amino-1-oxopropan-2-yl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(C107) (0.050 g, 0.091 mmol) was added acetonitrile (0.400 mL) and water(0.200 mL) to give a pale beige solution.[I,I-Bis(trifluoroacetoxy)iodo]benzene (0.039 g, 0.091 mmol, freshlyprepared as described in J. Org. Chem., 1984, 49, 4272-4276) was addedand the reaction was left to stir for 2.5 hours. The crude reactionmixture was adsorbed onto Celite® (5 g) and was purified by reversephase chromatography (C-18) using 10-100% acetonitrile/water as eluent.The title compound was isolated as an off-white solid (0.031 g, 66%): ¹HNMR (400 MHz, DMSO-d₆) δ 9.49 (d, J=7.3 Hz, 1H), 8.44 (s, 3H), 8.05 (s,1H), 7.97 (dt, J=8.4, 1.8 Hz, 1H), 7.94 (s, 2H), 7.61 (d, J=8.0 Hz, 1H),7.10 (dd, J=15.8, 9.1 Hz, 1H), 6.90 (d, J=15.8 Hz, 1H), 5.13 (p, J=6.6Hz, 1H), 4.90 (p, J=9.4 Hz, 1H), 1.45 (d, J=6.5 Hz, 3H); ¹⁹F NMR (376MHz, DMSO-d₆) δ −57.73, −67.93; ESIMS m/z 519 ([M−H]⁻).

The following compounds were prepared in accordance to the procedure inExample 16.

N—((R)-1-Aminopropyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide.hydrochloride(C111)

The title compound was prepared withN—((R)-1-amino-1-oxobutan-2-yl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide (C109) in place ofN—((R)-1-amino-1-oxopropan-2-yl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(C107) (0.910 g, 30%): 1H NMR (400 MHz, DMSO-d₆) δ 9.39 (dd, J=8.2, 1.4Hz, 1H), 8.57-8.43 (m, 3H), 8.05 (t, J=1.7 Hz, 1H), 7.98 (dd, J=8.1, 1.9Hz, 1H), 7.93 (s, 2H), 7.61 (d, J=8.0 Hz, 1H), 7.09 (dd, J=15.8, 9.1 Hz,1H), 6.89 (d, J=15.7 Hz, 1H), 4.91 (m, 2H), 1.81 (m, 2H), 0.93 (t, J=7.3Hz, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −57.80, −67.93; ESIMS m/z 533([M−H]⁻)

(E)-N-(Aminomethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide.hydrochloride(C112)

The title compound was prepared with(E)-N-(2-amino-2-oxoethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(C108) used in place ofN—((R)-1-amino-1-oxopropan-2-yl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(C107) (0.710 g, 50%): 1H NMR (400 MHz, DMSO-d₆) δ 9.27 (t, J=6.0 Hz,1H), 8.03 (d, J=1.6 Hz, 1H), 7.95 (dd, J=8.2, 1.9 Hz, 1H), 7.93 (s, 2H),7.57 (d, J=8.0 Hz, 1H), 7.09 (dd, J=15.8, 9.1 Hz, 1H), 6.89 (d, J=15.7Hz, 1H), 6.52 (s, 3H), 4.88 (p, J=9.3 Hz, 1H), 4.26 (d, J=6.0 Hz, 2H);¹⁹F NMR (376 MHz, DMSO-d₆) δ −57.74, −67.95; ESIMS m/z 505 ([M−H]⁻).

Example 17: Preparation ofN—((R)-1-hexanamidoethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F3)

Into a vial (4 mL) equipped with a magnetic stir vane were placed drydichloromethane (1.5 mL),N—((R)-1-aminoethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamidehydrochloride(C110) (0.100 g, 0.180 mmol) and hexanoyl chloride (0.0380 mL, 0.270mmol). To this solution was added 4-methylmorpholine (0.0500 mL, 0.450mmol). The resulting suspension was stirred overnight. The reactionmixture was diluted with ethyl acetate (20 mL) and citric acid (5%, 20mL). The layers were separated and the aqueous phase was extracted withadditional ethyl acetate. The pooled organic layers were dried withsodium sulfate, filtered, and concentrated. The resulting material waspurified by flash column chromatography using 0-100% ethylacetate/hexanes as eluent. The title compound was isolated as anoff-white foam (0.0860 g, 78%).

The following compounds were prepared in accordance to the procedure inExample 17.

N—((R)-1-(4-Methylpentanamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F4)

The title compound was prepared using 4-methylpentanoyl chloride andisolated as an off-white foam/glass (0.037 g, 34%).

N—((R)-1-Pentanamidoethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F5)

The title compound was prepared using pentanoyl chloride and isolated asan off-white foam/solid (0.028 g, 26%).

N—((R)-1-(3-Methylbutanamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F6)

The title compound was prepared using 3-methylbutanoyl chloride andisolated as an off-white foam (0.038 g, 35%).

N—((R)-1-(Cyclopropanecarboxamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F7)

The title compound was prepared using cyclopropanecarbonyl chloride andisolated as a colorless glass/foam (0.145 g, 55%).

N—((R)-1-(3-Methylbut-2-enamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F8)

The title compound was prepared using 3-methylbut-2-enoyl chloride andisolated as a colorless glass/foam (0.096 g, 55%).

Example 18: Preparation of4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(F2)

Into a vial (5 mL) equipped with a magnetic stir vane was placedN—((R)-1-aminoethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide.hydrochloride(C110) (0.117 g, 0.210 mmol) and 1,2-dichloroethane (3 mL).3,3,3-Trifluoropropanoyl chloride (0.0390 g, 0.266 mmol) was added andtwo minutes later 4-methylmorpholine (0.0690 mL, 0.631 mmol) was added.The reaction was vortexed 5 times over a 2 minute period. After thesecond vortex, the solution became cloudy. The reaction was left to stirfor an additional 1.5 hours. Purification by flash column chromatographyusing 0-100% ethyl acetate/hexanes as eluent. The title compound wasisolated as an off-white solid (0.060 g, 46%).

The following compounds were prepared in accordance to the procedure inExample 18.

4-((E)-4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(F1)

The title compound was prepared using 4,4,4-trifluorobutanoyl chlorideand isolated as an off-white solid (0.066 g, 65%).

4-((E)-4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)propyl)-2-(trifluoromethyl)benzamide(F12)

The title compound was prepared usingN—((R)-aminopropyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide.hydrochloride (C11) and4,4,4-trifluorobutanoyl chloride and isolated as a white sol id (0.084g, 49%).

(E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-((4,4,4-trifluorobutanamido)methyl)-2-(trifluoromethyl)benzamide(F13)

The title compound was prepared using(E)-N-(aminomethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide,hydrochloride (C112) and 4,4,4-trifluorobutanoyl chloride and isolatedas a pale yellow solid (0.040 g, 20%).

N—((S)-1-Pivalamidoethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F19)

The title compound was prepared using pivaloyl chloride and isolated asa white solid (0.104 g, 64%).

Example 19: Preparation ofN—((S)-1-(1-cyanocyclopropanecarboxamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F14)

Into a vial (5 mL) equipped with a magnetic stir vane was placed1-cyanocyclopropanecarboxylic acid (0.052 g, 0.47 mmol) and1,2-dichloroethane (1.3 mL). Oxalyl chloride (0.040 mL, 0.47 mmol) anddimethylformamide (˜1 drop) were added and the reaction was left to stirat room temperature for 3 hours.N—((R)-1-aminoethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide.hydrochloride(C110) (0.15 g, 0.27 mmol) and 4-methylmorpholine (0.089 mL, 0.81 mmol)were added and the reaction was capped, vortexed and left to stir.Purification by flash column chromatography using 0-100% ethylacetate/hexanes as eluent. The title compound was isolated as acolorless foam (0.135 g, 82%).

The following compounds were prepared in accordance to the procedure inExample 19.

N—((R)-1-(3,3-Dimethylbutanamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F15)

The title compound was prepared using 3,3-dimethylbutanoic acid andisolated as a colorless glass (0.109 g, 65%).

N—((R)-1-(4,4-Dimethylpentanamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F17)

The title compound was prepared using 4,4-dimethylpentanoic acid andisolated as a colorless foam (0.104 g, 61%).

4-((E)-4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-((1R)-1-(4,4,4-trifluoro-3-methylbutanamido)ethyl)-2-(trifluoromethyl)benzamide (F16)

The title compound was prepared using 4,4,4-trifluoro-3-methylbutanoicacid and isolated as a white solid (0.105 g, 59%).

N—((R)-1-(5,5-Dimethylhexanamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F18)

The title compound was prepared using 5,5-dimethylhexanoic acid andisolated as a white solid (0.100 g, 57%).

N—((R)-1-(4,4,4-Trifluoro-2-methylbutanamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(P30)

Isolated as a colorless glass (0.096 g, 24%).

N—((S)-1-(3,3,3-Trifluoro-2,2-dimethylpropanamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(P33)

Isolated as a white solid (0.101 g, 51%).

Example 20: Preparation ofN—((R)-1-(3-cyanopropanamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F9)

Into a vial (4 mL) equipped with a stir vane was placed 3-cyanopropanoicacid (0.080 g, 0.81 mmol)),(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbeniumhexafluorophosphate (0.37 g, 0.86 mmol), and 4-methylmorpholine (0.14 g,1.3 mmol). Dimethylformamide (1 mL) was added and the reaction wasstirred at room temperature for 5 minutes.N—((R)-1-Aminoethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide.hydrochloride(C110) (0.30 g, 0.54 mmol) was dissolved in dimethylformamide (0.5 mL)and was added drop-wise. The mixture was then stirred at roomtemperature overnight. The resulting solution was diluted with ethylacetate (˜20 mL) and was washed with water. The organic layer was driedwith sodium sulfate, filtered, and concentrated. The resulting materialwas purified via flash column chromatography using 35% ethylacetate/hexanes as eluent to provide the title compound as a brownglass/foam (0.073 g, 23%).

The following compounds were prepared in accordance to the procedure inExample 20.

4-((E)-4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(5,5,5-trifluoropentanamido)ethyl)benzamide(F10)

The title compound was prepared using 5,5,5-trifluoropentanoic acid andisolated as a colorless glass/foam (0.173 g, 49%).

N—((R)-1-(2-Cyanoacetamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(F11)

The title compound was prepared using 2-cyanoacetic acid and isolated asan off-white foam/glass (0.132 g, 42%).

Example 21: Preparation of (E)-tert-butylmethyl(2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamido)ethyl)carbamate(C113)

Into a round-bottomed flask (250 mL) was added(E)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C92) (0.75 g, 1.6 mmol), tert-butyl(2-aminoethyl)(methyl)carbamate (0.56 mL, 3.1 mmol),1H-benzo[d][1,2,3]triazol-1-ol hydrate (0.24 g, 1.6 mmol), and2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate(V) (0.60 g, 1.6 mmol) and acetonitrile (27 mL) undernitrogen. N-Ethyl-N-isopropylpropan-2-amine (0.55 mL, 3.1 mmol) was thenadded dropwise and the reaction was allowed to stir at room temperatureovernight. The reaction mixture was then filtered through a silica gelfrit, concentrated, purified by flash column chromatography using ethylacetate/hexanes as eluent to provide the title compound as a light brownfoam (0.40 g, 38%): ¹H NMR (400 MHz, CDCl₃) δ 7.66 (s, 1H), 7.57-7.46(m, 2H), 7.42 (s, 2H), 6.74 (s, 1H), 6.61 (d, J=15.9 Hz, 1H), 6.42 (dd,J=15.9, 7.8 Hz, 1H), 4.12 (p, J=8.4 Hz, 1H), 3.60 (dt, J=6.1, 4.7 Hz,2H), 3.48 (d, J=6.2 Hz, 2H), 2.92 (s, 3H), 1.40 (s, 9H); ¹⁹F NMR (376MHz, CDCl₃) δ −59.31, −68.58; ESIMS m/z 633 ([M−H]⁻).

Example 22: Preparation of(E)-N-(2-(methylamino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide.hydrochloride(C114)

Into a round-bottomed flask (100 mL) under nitrogen was added(E)-tert-butylmethyl(2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamido)ethyl)carbamate(C113) (0.770 g, 1.22 mmol) and dichloromethane (1.39 mL). Hydrochloricacid (4 M in dioxane) (1.39 mL) was then added dropwise to the solutionand the solution was allowed to stir at room temperature overnight. Thereaction was concentrated to provide the title compound as a brown foam(0.500 g, 51%): ¹H NMR (400 MHz, MeOH-d₄) δ 7.90-7.81 (m, 2H), 7.70 (s,2H), 7.63 (d, J=8.0 Hz, 1H), 6.91-6.75 (m, 2H), 4.64-4.50 (m, 1H), 3.66(s, 4H), 2.78 (s, 3H) (NH not observed); ¹⁹F NMR (376 MHz, MeOH-d₄)5-60.51, −70.47; ESIMS m/z 533 ([M−H]⁻).

Example 23: Preparation of(E)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(2-(3,3,3-trifluoro-N-methylpropanamido)ethyl)-2-(trifluoromethyl)benzamide (F20)

Into a round-bottomed flask (100 mL) was added the1H-benzo[d][1,2,3]triazol-1-ol hydrate (0.040 g, 0.26 mmol),2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate(V) (0.10 g, 0.26 mmol),(E)-N-(2-(methylamino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide.hydrochloride(C114) (0.15 g, 0.26 mmol), 3,3,3-trifluoropropanoic acid (0.046 mL,0.53 mmol), and acetonitrile (4.5 mL) under nitrogen. This was thenfollowed by dropwise addition of N-ethyl-N-isopropylpropan-2-amine (0.14mL, 0.79 mmol). The resulting solution was allowed to stir overnight atroom temperature. The reaction mixture was filtered through silica gelfrit, concentrated, and then purified via flash column chromatography toprovide the title compound as a brown glass (0.094 g, 50%).

Example 24: Preparation of(E)-N-(2-(methylamino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(C115)

Into a round-bottomed flask (100 mL) containing(E)-N-(2-(methylamino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide.hydrochloride(C114) (0.60 g, 1.1 mmol) was added dichloromethane (20 mL) followed bysaturated sodium bicarbonate (10 mL). This mixture was allowed to stirfor 10 minutes. The solution was extracted with dichloromethane. Thecombined organic layers were dried, concentrated, and purified by flashcolumn chromatography using methanol/dichloromethane as eluent toprovide the title compound as a yellow foam (0.30 g, 51%): ¹H NMR (400MHz, CDCl₃) δ 7.65 (s, 1H), 7.55 (d, J=7.9 Hz, 1H), 7.42 (d, J=3.3 Hz,3H), 6.61 (d, J=15.9 Hz, 1H), 6.42 (dd, J=15.9, 7.9 Hz, 1H), 4.12 (p,J=8.7 Hz, 1H), 3.59 (q, J=5.4 Hz, 2H), 2.88 (t, J=5.5 Hz, 2H), 2.47 (s,3H) (NH not observed); ¹⁹F NMR (376 MHz, CDCl₃) δ −59.11, −68.60; ESIMSm/z 535 ([M+H]⁺).

Example 25: Preparation of(E)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(2-(2,2,2-trifluoro-N-methylacetamido)ethyl)-2-(trifluoromethyl)benzamide(F21)

Into a round-bottomed flask (100 mL) was added the(E)-N-(2-(methylamino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(C115) (0.125 g, 0.234 mmol), tetrahydrofuran (0.781 mL), anddichloromethane (0.781 mL) under nitrogen. This was followed by thedropwise addition of the trifluoroacetic anhydride (0.0350 mL, 0.246mmol). The reaction was then allowed to stir at room temperature for 18hours. The mixture was diluted with dichloromethane, concentrated, andpurified via flash column chromatography using ethyl acetate/hexanes aseluent to provide the title compound as a very light yellow glass/foam(0.0720 g, 46%).

Example 26: Preparation of (E)-tert-butyl1-methyl-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoyl)hydrazinecarboxylate(C116)

To N-ethyl-N-isopropylpropan-2-amine (1.21 mL, 7.08 mmol),benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (1.35g, 2.60 mmol), tert-butyl N-amino-N-methyl-carbamate (0.380 g, 2.60mmol) was added(E)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoicacid (C92) (1.00 g, 2.36 mmol) in dichloromethane (5 mL). The reactionwas stirred at room temperature for 12 hours. The reaction mixture waspoured into water and extracted with dichloromethane (20 mL). Theseparated organic layer was washed with water, brine, dried over sodiumsulfate, filtered, and concentrated. The residue was purified via flashcolumn chromatography using 30% ethyl acetate/petroleum ether as eluentto provide the title compound as a colorless liquid (0.750 g, 49%): IR(thin film) 3418, 2928, 1714, 1160, 865 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆)δ 10.4 (s, 1H), 7.89 (s, 2H), 7.48-7.43 (m, 2H), 7.33 (d, J=8.0 Hz, 1H),6.90 (dd, 3=15.6, 8.8 Hz, 1H), 6.76 (d, J=15.6 Hz, 1H), 4.86-4.82 (m,1H), 2.38 (s, 3H), 1.45 (s, 9H); ESIMS m/z 603 ([M−H]⁻).

Example 27: Preparation of(E)-N′-methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzohydrazide.hydrochloride(C117)

To (E)-tert-butyl1-methyl-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoyl)hydrazinecarboxylate(C116) (1.0 g, 1.7 mmol) in dioxane (10 mL) was added hydrochloric acid(4 M in dioxane) (10 mL). The solution was allowed to stir at roomtemperature for 2 hours. The reaction was concentrated, washed withpentane, filtered, and dried to provide the title compound as a yellowsolid (0.80 g, 89%): ¹H NMR (300 MHz, DMSO-d₆) δ 11.30 (bs, 2H), 8.09(bs, 1H), 7.97 (d, J=6.6 Hz, 2H), 7.92 (s, 1H), 7.65 (d, J=8.4 Hz, 2H),7.14 (dd, J=15.9, 8.7 Hz, 1H), 6.91 (d, J=15.9 Hz, 1H), 4.90 (t, J=6.9Hz, 1H), 2.73 (bs, 3H); ESIMS m/z 505 ([M+H]⁺).

Example 28: Preparation of(E)-N′-methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)-N′-(3,3,3-trifluoropropanoyl)benzohydrazide(F22)

To N-ethyl-N-isopropylpropan-2-amine (0.14 mL, 0.83 mmol),benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (0.16g, 0.30 mmol) was added(E)-N′-methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzohydrazide.hydrochloride(C117) (0.15 g, 0.28 mmol) and 3,3,3-trifluoropropanoic acid (0.046 mL,0.53 mmol) in dichloromethane (5 mL). The reaction was stirred at roomtemperature for 6 hours. The reaction mixture was then diluted withdichloromethane and washed with water. The organic layer was dried oversodium sulfate, filtered, and concentrated. The residue was purified viaflash column chromatography using 20% ethyl acetate/petroleum ether aseluent to provide the title compound as a pale yellow gum (0.15 g, 86%).

The following compounds were prepared in accordance to the procedure inExample 28.

(E)-N′-Methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N′-(4,4,4-trifluorobutanoyl)-2-(trifluoromethyl)benzohydrazide(F23)

The title compound was prepared using 4,4,4-trifluorobutanoic acid andisolated as a pale yellow gum (0.21 g, 91%).

Example 29: Preparation of 3,5-Dibromo-4-chlorobenzaldehyde (C121)

Step 1. Methyl 4-amino-3,5-dibromobenzoate (C118)

Concentrated sulfuric acid (1.35 mL, 25.5 mmol) was added dropwise to astirred solution of 4-amino-3,5-dibromobenzoic acid (5.00 g, 17.0 mmol)in methanol (50 mL) at ambient temperature and the reaction mixture wasthen stirred at 80° C. for 8 hours. The reaction mixture was allowed tocool to ambient temperature, volatiles were evaporated, ice-water wasadded to the residue, and extracted with ethyl acetate. The organiclayer was washed with aqueous sodium bicarbonate solution followed bybrine and water, dried (sodium sulfate), filtered, and concentrated toafford the title compound as an off white solid (5.00 g, 95%): ¹H NMR(300 MHz, DMSO-d₆) δ 7.91 (s, 2H), 6.20 (bs, 2H), 3.78 (s, 3H); ESIMSm/z 307 ([M]⁺); IR (thin film) 3312, 2953, 1726, 595 cm⁻¹.

Step 2. Methyl 3,5-dibromo-4-chlorobenzoate (C119)

Copper(II) chloride (2.82 g, 21.0 mmol) in acetonitrile (30 mL) wasstirred at 80° C. for 30 minutes. tert-Butylnitrite (2.70 mL, 23.0 mmol)was then added dropwise at the same temperature and the mixture wasstirred for another 10 minutes. Methyl 4-amino-3,5-dibromobenzoate(C118) (5.00 g, 16.0 mmol) in acetonitrile (30 mL) was added dropwise tothe reaction mixture and stirred at 80° C. for 30 minutes. The reactionmixture was allowed to cool to ambient temperature and an aqueousammonia solution (20 mL) was added to the reaction mixture followed byextraction with petroleum ether. The organic layer was washed with brinefollowed by water, dried (sodium sulfate), filtered, and concentrated toafford the title compound as an off white solid (4.50 g, 84%): ¹H NMR(300 MHz, DMSO-d₆) δ 8.21 (s, 2H), 3.94 (s, 3H); ESIMS m/z 326 ([M]⁺);IR (thin film) 1732, 746 cm⁻¹.

Step 3. (3,5-Dibromo-4-chlorophenyl)methanol (C120)

Sodium borohydride (1.53 g, 40.7 mmol) was added portionwise to astirred solution of methyl 3,5-dibromo-4-chlorobenzoate (C119) (4.45 g,13.6 mmol) in methanol (50 mL) at 0° C. The reaction mixture was thenstirred at ambient temperature for 8 hours. The volatiles wereevaporated and the residue was diluted with dichloromethane and washedwith brine followed by water. The organic layer was dried (sodiumsulfate), filtered, and concentrated to afford the title compound as anoff white solid (3.30 g, 80%): ¹H NMR (300 MHz, DMSO-d₆) δ 7.71 (s, 2H),5.49 (bs, 1H), 4.48 (d, J=4.5 Hz, 2H); ESIMS m/z 298 ([M]⁺); IR (thinfilm) 3460, 747, 534 cm⁻¹.

Step 4. 3,5-Dibromo-4-chlorobenzaldehyde (C121)

Pyridinium chlorochormate (3.44 g, 15.9 mmol) was added in one portionto a stirred solution of (3,5-dibromo-4-chlorophenyl)methanol (C120)(3.2 g, 11.0 mmol) in chloroform (40 mL) at ambient temperature and thereaction mixture was stirred overnight. The reaction mixture wasfiltered through Celite®, the Celite® pad was washed with chloroform,and the filtrate was concentrated to afford the title compound as an offwhite solid (2.00 g, 62%): mp 110-113° C.; ¹H NMR (300 MHz, DMSO-d₆) δ9.93 (s, 1H), 8.27 (s, 2H); ESIMS m/z 297 ([M]⁺).

The following compounds were prepared in accordance to the procedures inExample 29.

4-Bromo-3,5-dichlorobenzaldehyde (C125)

Step 1. Methyl 4-amino-3,5-dichlorobenzoate (C122)

The title compound was isolated as a white solid (7.5 g, 70%): ¹H NMR(300 MHz, DMSO-d₆) δ 8.05 (s, 2H), 3.96 (s, 3H); ESIMS m/z 282 ([M]⁺);IR (KBr): 1733, 762, 514 cm⁻¹.

Step 2. Methyl 4-bromo-3,5-dichlorobenzoate (C123)

The title compound was isolated as an off white solid (7.5 g, 77%): ¹HNMR (300 MHz, DMSO-d₆) δ 8.02 (s, 2H), 3.94 (s, 3H); ESIMS m/z 282([M]⁺); IR (thin film) 1733, 762, 514 cm⁻¹.

Step 3. (4-Bromo-3,5-dichlorophenyl)methanol (C124)

The title compound was isolated as an off white solid which was taken tonext step without purification.

Step 4. 4-Bromo-3,5-dichlorobenzaldehyde (C125)

The title compound was isolated as an off white solid (3.5 g, 67%): mp125-128° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.96 (s, 1H), 8.10 (s, 2H);ESIMS m/z 252 ([M]⁺).

Example 30: Preparation of4-((E)-3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(P24)

To a vial (50 mL) under a nitrogen atmosphere was added(E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (C88) (0.306 g, 0.626 mmol) and 1,2-dichloroethane (2 mL). Oxalyldichloride (0.100 mL, 1.17 mmol) and N,N-dimethylformamide (0.00400 mL,0.0510 mmol) were added, and the resulting suspension was stirred for 1hour. The reaction mixture was concentrated to remove any excess oxalylchloride. The resulting orange oil was diluted with 1,2-dichloroethane(5 mL) and added to a vial (25 mL) containing(S)—N-(1-aminoethyl)-3,3,3-trifluoropropanamide hydrochloride (CA5)(0.168 g, 0.814 mmol). The reaction mixture was vortexed, and4-methylmorpholine (0.172 mL, 1.57 mmol) was added. The reaction vialwas capped and vortexed several times over a 1 minute period. Thereaction mixture was allowed to stir with occasional vortexing for 1hour. The reaction mixture was concentrated under a stream of nitrogengas, dissolved in N,N-dimethylformamide:water (5:1, 3.2 mL), andpartially purified via preparative C-18 reverse phase HPLC purificationusing 5-95% acetonitrile (0.1% acetic acid) and water (0.1% acetic acid)as eluent. The obtained material was dissolved in methanol containing anexcess of Amberlite IRA-65 weak anion exchange resin in the free baseform (IRA-67 free base), and the mixture was vortexed and left to standfor 1 hour. The mixture was gravity filtered, and the resin was washedwith excess methanol. The filtrate was concentrated to provide thedesired compound as a white solid (0.172 g, 39%).

The following compounds were prepared in accordance to the procedures inExample 30.

4-((E)-3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(P1)

Isolated as an amber glass (0.041 g, 10%).

4-((E)-3-(3,5-Dibromo-4-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(P2)

Isolated as an amber glass (0.223 g, 55%).

4-((E)-3-(3,5-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(P3)

Isolated as a brown amorphous solid (0.226 g, 52%).

4-((E)-3-(4-Bromo-3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(P4)

Isolated as a brown amorphous solid (0.226 g, 52%).

4-((E)-3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methyl-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(P5)

Isolated as a pale yellow glass (0.215 g, 49%).

4-((E)-3-(3,5-Dibromo-4-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methyl-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(P6)

Isolated as a pale orange glass (0.211 g, 49%).

4-((E)-3-(3,5-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methyl-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(P7)

Isolated as a brown amorphous solid (0.226 g, 54%).

4-((E)-3-(4-Bromo-3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methyl-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(P8)

Isolated as a pale yellow solid (0.148 g, 35%).

4-((E)-3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(P9)

Isolated as a colorless glass (0.036 g, 8%).

4-((E)-3-(3,5-Dibromo-4-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(P10)

Isolated as a pale yellow glass (0.171 g, 39%).

4-((E)-3-(3,5-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(P11)

Isolated as an amber glass (0.181 g, 39%).

4-((E)-3-(4-Bromo-3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)-2-(trifluoromethyl)benzamide(P12)

Isolated as an orange glass (0.135 g, 29%).

4-((E)-3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methyl-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)benzamide(P13)

Isolated as a light yellow solid (0.197 g, 42%).

4-((E)-3-(3,5-Dibromo-4-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methyl-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)benzamide(P14)

Isolated as a white solid (0.104 g, 16%).

4-((E)-3-(3,5-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methyl-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)benzamide(P15)

Isolated as a beige solid (0.150 g, 33%).

4-((E)-3-(4-Bromo-3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methyl-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)benzamide(P16)

Isolated as a white solid (0.122 g, 20%).

2-Methyl-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(P22)

Isolated as a beige solid (0.241 g, 52%).

2-Methyl-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)benzamide(P25)

Isolated as a beige solid (0.157 g, 32%).

2-Bromo-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorobutanamido)ethyl)benzamide(P27)

Isolated as a pale yellow solid (0.110 g, 24%).

N—((R)-1-(3-(Methylthio)propanamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(P53)

Isolated as a white foam (0.225 g, 36%).

N—((S)-1-(2-(Methylthio)acetamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(P54)

Isolated as a white foam (0.353 g, 55%).

4-((E)-4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(4,4,4-trifluorbutanamido)ethyl)benzamide(FC1)

Isolated as a yellow foam (0.0423 g, 40%, approximately 30% pure).

4-((E)-4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N—((R)-1-(3,3,3-trifluoropropanamido)ethyl)benzamide(FC2)

Isolated as a white solid (0.052 g, 47%).

Example 31: Preparation ofN—((R)-1-(3-(methylsulfonyl)propanamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(P47) andN-((1R)-1-(3-(methylsulfinyl)propanamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(P49)

To a vial (25 mL) was addedN—((R)-1-(3-(methylthio)propanamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide (P53) (0.150 g, 0.241 mmol),sodium perborate tetrahydrate (0.0557 g, 0.362 mmol), and acetic acid (5mL). The vial was capped, and the reaction was stirred and heated at 55°C. overnight. The reaction mixture was concentrated under a stream ofnitrogen gas. Purification by flash column chromatography using 20-100%ethyl acetate/hexanes followed by 0-40% methanol/dichloromethane aseluent provided the title compound (P47) as a colorless glass (0.0630 g,72%) and (P49) as a colorless glass (0.0360 g, 42%).

The following compounds were prepared in accordance to the procedures inExample 31.

N-((1S)-1-(2-(Methylsulfinyl)acetamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(P36)

Isolated as a colorless glass (0.054 g, 34%).

N—((S)-1-(2-(Methylsulfonyl)acetamido)ethyl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(P43)

Isolated as a colorless glass (0.138 g, 85%).

Example 32: Preparation of(S)—N-(1-aminoethyl)-4,4,4-trifluorobutanamide hydrochloride (CA4)

(S)—N-(1-Amino-1-oxopropan-2-yl)-4,4,4-trifluorobutanamide (CA6) (3.00g, 14.1 mmol) was dissolved in water (21 mL) and acetonitrile (21 mL),after which [I,I-bis(trifluoroacetoxy)iodo]benzene (6.08 g, 14.1 mmol)was added. The reaction mixture was stirred in a flask wrapped inaluminum foil overnight. The reaction mixture was then poured intohydrochloric acid (1 N, 35 mL) and diethyl ether (35 mL). The organiclayer was separated, and the aqueous layer was azeotroped (2×125 mL)with isopropanol. Purification by reverse phase flash columnchromatography using 20% acetonitrile/water as eluent provided the titlecompound as a white, highly hygroscopic solid (1.50 g, 48%): ¹H NMR (400MHz, DMSO-d₆) δ 9.11 (d, J=7.4 Hz, 1H), 8.36 (s, 3H), 4.94 (p, J=6.6 Hz,1H), 2.66-2.32 (m, 4H), 1.40 (d, J=6.5 Hz, 3H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ −65.19; ESIMS m/z 185 ([M+H]⁺).

The following compound was prepared in accordance to the procedures inExample 32.

(S)—N-(1-Aminoethyl)-3,3,3-trifluoropropanamide hydrochloride (CA5)

Isolated as an off-white solid (2.8 g, 90%): mp 125° C. (dec.); ¹H NMR(400 MHz, DMSO-d₆) δ 9.47 (d, J=7.3 Hz, 1H), 8.48 (s, 3H), 4.96 (p,J=6.6 Hz, 1H), 3.44 (m, 2H), 1.42 (d, J=6.5 Hz, 3H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ −61.28.

Example 33: Preparation of(S)—N-(1-amino-1-oxopropan-2-yl)-4,4,4-trifluorobutanamide (CA6)

To a round bottomed flask (500 mL) was added sodium bicarbonate(saturated solution, 54.6 mL, 60.1 mmol) and (S)-2-aminopropanamidehydrochloride (3.74 g, 30.0 mmol). The solution was allowed to stiruntil gas evolution ceased, after which time trifluoroethanol (54.6 mL)was added. 3,3,3-Trifluoropropanoyl chloride (2.81 ml, 27.3 mmol) wasadded in small portions (gas evolution). Addition rate was determined bythe rate of gas evolution. After addition was complete, the reactionmixture was left to stir open to air at room temperature overnight.Hydrochloric acid (2 M, ˜15 mL) was added until gas evolution ceased,and the solution was concentrated. The resulting slurry was diluted withethyl acetate and water, the layers were separated and the aqueous layerwas extracted with ethyl acetate (3×100 mL). The resulting organic layerwas dried over sodium sulfate, filtered, and concentrated to provide thetitle compound as a white solid (3.30 g, 55%): ¹H NMR (300 MHz, DMSO-d₆)δ 8.15 (d, J=7.6 Hz, 1H), 7.33 (s, 1H), 6.98 (s, 1H), 4.21 (p, J=7.2 Hz,1H), 2.49-2.34 (m, 4H), 1.19 (d, J=7.1 Hz, 3H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ −61.46; ESIMS m/z 197 ([M−H]⁻).

The following compound was prepared in accordance to the procedures inExample 33.

(S)—N-(1-Amino-1-oxopropan-2-yl)-3,3,3-trifluoropropanamide (CA7)

Isolated as a white solid (1.5 g, 39%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.38(d, J=7.6 Hz, 1H), 7.43 (s, 1H), 7.04 (s, 1H), 4.25 (p, J=7.1 Hz, 1H),3.32 (q, J=11.3 Hz, 2H), 1.20 (d, J=7.1 Hz, 3H); ¹⁹F NMR (376 MHz,DMSO-d₆) δ −65.18.

The following prophetic molecules could be made in accordance with theprocedures disclosed above:

TABLE 1 Structure and Preparation Method for P Series Compounds Prep.according to example No. Structure or scheme: P1

Example 18 P2

Example 18 P3

Example 18 P4

Example 18 P5

Example 18 P6

Example 18 P7

Example 18 P8

Example 18 P9

Example 18 P10

Example 18 P11

Example 18 P12

Example 18 P13

Example 18 P14

Example 18 P15

Example 18 P16

Example 18 P17

Scheme 4 P18

Scheme 4 P19

Scheme 4 P20

Scheme 4 P21

Scheme 4 P22

Example 18 P23

Example 18 P24

Example 18 P25

Example 18 P26

Example 18 P27

Example 18 P28

Examples 18, 19, 20, or 21 P29

Examples 18, 19, 20, or 21 P30

Examples 18, 19, 20, or 21 P31

Examples 18, 19, 20, or 21 P32

Examples 18, 19, 20, or 21 P33

Examples 18, 19, 20, or 21 P34

Examples 18, 19, 20, or 21 P35

Examples 18, 19, 20, or 21 P36

Examples 18, 19, 20, or 21 P37

Examples 18, 19, 20, or 21 P38

Examples 18, 19, 20, or 21 P39

Examples 18, 19, 20, or 21 P40

Examples 18, 19, 20, or 21 P41

Examples 18, 19, 20, or 21 P42

Examples 18, 19, 20, or 21 P43

Examples 18, 19, 20, or 21 P44

Examples 18, 19, 20, or 21 P45

Examples 18, 19, 20, or 21 P46

Examples 18, 19, 20, or 21 P47

Examples 18, 19, 20, or 21 P48

Examples 18, 19, 20, or 21 P49

Examples 18, 19, 20, or 21 P50

Examples 18, 19, 20, or 21 P51

Examples 18, 19, 20, or 21 P52

Examples 18, 19, 20, or 21 P53

Examples 18, 19, 20, or 21 P54

Examples 18, 19, 20, or 21

Example A: Bioassays on Beet Armyworm (“BAW”) and Cabbage Looper (“CL”)

BAW has few effective parasites, diseases, or predators to lower itspopulation. BAW infests many weeds, trees, grasses, legumes, and fieldcrops. In various places, it is of economic concern upon asparagus,cotton, corn, soybeans, tobacco, alfalfa, sugar beets, peppers,tomatoes, potatoes, onions, peas, sunflowers, and citrus, among otherplants. CEW is known to attack corn and tomatoes, but it also attacksartichoke, asparagus, cabbage, cantaloupe, collards, cowpeas, cucumbers,eggplant, lettuce, lima beans, melon, okra, peas, peppers, potatoes,pumpkin, snap beans, spinach, squash, sweet potatoes, and watermelon,among other plants. CEW is also known to be resistant to certaininsecticides. CL feeds on a wide variety of cultivated plants and weeds.It feeds readily on crucifers, and has been reported damaging broccoli,cabbage, cauliflower, Chinese cabbage, collards, kale, mustard, radish,rutabaga, turnip, and watercress. Other vegetable crops injured includebeet, cantaloupe, celery, cucumber, lima bean, lettuce, parsnip, pea,pepper, potato, snap bean, spinach, squash, sweet potato, tomato, andwatermelon. CL is also known to be resistant to certain insecticides.Consequently, because of the above factors control of these pests isimportant. Furthermore, molecules that control these pests are useful incontrolling other pests.

Certain molecules disclosed in this document were tested against BAW andCEW and CL using procedures described in the following examples. In thereporting of the results, the “BAW & CL Rating Table” was used (SeeTable Section).

Bioassays on BAW (Spodoptera exigua)

Bioassays on BAW were conducted using a 128-well diet tray assay. one tofive second instar BAW larvae were placed in each well (3 mL) of thediet tray that had been previously filled with 1 mL of artificial dietto which 50 μg/cm² of the test compound (dissolved in 50 μL of 90:10acetone-water mixture) had been applied (to each of eight wells) andthen allowed to dry. Trays were covered with a clear self-adhesivecover, and held at 25° C., 14:10 light-dark for five to seven days.Percent mortality was recorded for the larvae in each well; activity inthe eight wells was then averaged. The results are indicated in thetables entitled “Table ABC: Assay Results (F)”, “Table ABCD: AssayResults (C)”, and “Table ABCDE: Assay Results (P)” (See Table Section).

Bioassays on CL (Trichoplusia ni)

Bioassays on CL were conducted using a 128-well diet tray assay. One tofive second instar CL larvae were placed in each well (3 mL) of the diettray that had been previously filled with 1 mL of artificial diet towhich 50 μg/cm² of the test compound (dissolved in 50 μL of 90:10acetone-water mixture) had been applied (to each of eight wells) andthen allowed to dry. Trays were covered with a clear self-adhesivecover, and held at 25° C., 14:10 light-dark for five to seven days.Percent mortality was recorded for the larvae in each well; activity inthe eight wells was then averaged. The results are indicated in thetable entitled “Table ABC: Assay Results (F)”, “Table ABCD: AssayResults (C)”, and “Table ABCDE: Assay Results (P)” (See Table Section).

Example B: Bioassays on Green Peach Aphid (“GPA”) (Myzus Persicae)

GPA is the most significant aphid pest of peach trees, causing decreasedgrowth, shriveling of the leaves, and the death of various tissues. Itis also hazardous because it acts as a vector for the transport of plantviruses, such as potato virus Y and potato leafroll virus to members ofthe nightshade/potato family Solanaceae, and various mosaic viruses tomany other food crops. GPA attacks such plants as broccoli, burdock,cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce,macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, andzucchini, among other plants. GPA also attacks many ornamental cropssuch as carnation, chrysanthemum, flowering white cabbage, poinsettia,and roses. GPA has developed resistance to many pesticides.

Certain molecules disclosed in this document were tested against GPAusing procedures described in the following example. In the reporting ofthe results, the “GPA & YFM Rating Table” was used (See Table Section).

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) trueleaves, were used as test substrate. The seedlings were infested with20-50 GPA (wingless adult and nymph stages) one day prior to chemicalapplication. Four pots with individual seedlings were used for eachtreatment. Test compounds (2 mg) were dissolved in 2 mL of acetone/MeOH(1:1) solvent, forming stock solutions of 1000 ppm test compound. Thestock solutions were diluted 5× with 0.025% Tween 20 in water to obtainthe solution at 200 ppm test compound. A hand-held aspirator-typesprayer was used for spraying a solution to both sides of cabbage leavesuntil runoff. Reference plants (solvent check) were sprayed with thediluent only containing 20% by volume of acetone/MeOH (1:1) solvent.Treated plants were held in a holding room for three days atapproximately 25° C. and ambient relative humidity (RH) prior tograding. Evaluation was conducted by counting the number of live aphidsper plant under a microscope. Percent Control was measured by usingAbbott's correction formula (W. S. Abbott, “A Method of Computing theEffectiveness of an Insecticide” J. Econ. Entomol. 18 (1925), pp.265-267) as follows. Corrected % Control=100*(X−Y)/X where X=No. of liveaphids on solvent check plants and Y=No. of live aphids on treatedplants. The results are indicated in the table entitled “Table ABC:Assay Results (F)” and “Table ABCD: Assay Results (C)” (See TableSection).

Example C: Bioassays on Yellow Fever Mosquito “YFM” (Aedes aegypti)

YFM prefers to feed on humans during the daytime and is most frequentlyfound in or near human habitations. YFM is a vector for transmittingseveral diseases. It is a mosquito that can spread the dengue fever andyellow fever viruses. Yellow fever is the second most dangerousmosquito-borne disease after malaria. Yellow fever is an acute viralhemorrhagic disease and up to 50% of severely affected persons withouttreatment will die from yellow fever. There are an estimated 200,000cases of yellow fever, causing 30,000 deaths, worldwide each year.Dengue fever is a nasty, viral disease; it is sometimes called“breakbone fever” or “break-heart fever” because of the intense pain itcan produce. Dengue fever kills about 20,000 people annually.Consequently, because of the above factors control of this pest isimportant. Furthermore, molecules that control this pest (YFM), which isknown as a sucking pest, are useful in controlling other pests thatcause human and animal suffering.

Certain molecules disclosed in this document were tested against YFMusing procedures described in the following paragraph. In the reportingof the results, the “GPA & YFM Rating Table” was used (See TableSection).

Master plates containing 400 μg of a molecule dissolved in 100 μL ofdimethyl sulfoxide (DMSO) (equivalent to a 4000 ppm solution) are used.A master plate of assembled molecules contains 15 μL per well. To thisplate, 135 μL of a 90:10 water:acetone mixture is added to each well. Arobot (Biomek® NXP Laboratory Automation Workstation) is programmed todispense 15 μL aspirations from the master plate into an empty 96-wellshallow plate (“daughter” plate). There are 6 reps (“daughter” plates)created per master. The created daughter plates are then immediatelyinfested with YFM larvae. The day before plates are to be treated,mosquito eggs are placed in Millipore water containing liver powder tobegin hatching (4 g. into 400 mL). After the daughter plates are createdusing the robot, they are infested with 220 μL of the liverpowder/larval mosquito mixture (about 1 day-old larvae). After platesare infested with mosquito larvae, a non-evaporative lid is used tocover the plate to reduce drying. Plates are held at room temperaturefor 3 days prior to grading. After 3 days, each well is observed andscored based on mortality. The results are indicated in the tableentitled “Table ABC: Assay Results (F)” and “Table ABCD: Assay Results(C)” (See Table Section).

Pesticidally Acceptable Acid Addition Salts, Salt Derivatives, Solvates,Ester Derivatives, Polymorphs, Isotopes and Radionuclides

Molecules of Formula One may be formulated into pesticidally acceptableacid addition salts. By way of a non-limiting example, an amine functioncan form salts with hydrochloric, hydrobromic, sulfuric, phosphoric,acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic,succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic,benzenesulfonic, methanesulfonic, ethanesulfonic,hydroxymethanesulfonic, and hydroxyethanesulfonic acids. Additionally,by way of a non-limiting example, an acid function can form saltsincluding those derived from alkali or alkaline earth metals and thosederived from ammonia and amines. Examples of preferred cations includesodium, potassium, and magnesium.

Molecules of Formula One may be formulated into salt derivatives. By wayof a non-limiting example, a salt derivative can be prepared bycontacting a free base with a sufficient amount of the desired acid toproduce a salt. A free base may be regenerated by treating the salt witha suitable dilute aqueous base solution such as dilute aqueous sodiumhydroxide (NaOH), potassium carbonate, ammonia, and sodium bicarbonate.As an example, in many cases, a pesticide, such as 2,4-D, is made morewater-soluble by converting it to its dimethylamine salt.

Molecules of Formula One may be formulated into stable complexes with asolvent, such that the complex remains intact after the non-complexedsolvent is removed. These complexes are often referred to as “solvates.”However, it is particularly desirable to form stable hydrates with wateras the solvent.

Molecules of Formula One may be made into ester derivatives. These esterderivatives can then be applied in the same manner as the inventiondisclosed in this document is applied.

Molecules of Formula One may be made as various crystal polymorphs.Polymorphism is important in the development of agrochemicals sincedifferent crystal polymorphs or structures of the same molecule can havevastly different physical properties and biological performances.

Molecules of Formula One may be made with different isotopes. Ofparticular importance are molecules having ²H (also known as deuterium)in place of ¹H.

Molecules of Formula One may be made with different radionuclides. Ofparticular importance are molecules having ¹⁴C.

Stereoisomers

Molecules of Formula One may exist as one or more stereoisomers. Thus,certain molecules can be produced as racemic mixtures. It will beappreciated by those skilled in the art that one stereoisomer may bemore active than the other stereoisomers. Individual stereoisomers maybe obtained by known selective synthetic procedures, by conventionalsynthetic procedures using resolved starting materials, or byconventional resolution procedures. Certain molecules disclosed in thisdocument can exist as two or more isomers. The various isomers includegeometric isomers, diastereomers, and enantiomers. Thus, the moleculesdisclosed in this document include geometric isomers, racemic mixtures,individual stereoisomers, and optically active mixtures. It will beappreciated by those skilled in the art that one isomer may be moreactive than the others. The structures disclosed in the presentdisclosure are drawn in only one geometric form for clarity, but areintended to represent all geometric forms of the molecule.

Combinations

Molecules of Formula One may also be used in combination (such as, in acompositional mixture, or a simultaneous or sequential application) withone or more compounds having acaricidal, algicidal, avicidal,bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal,nematicidal, rodenticidal, or virucidal properties. Additionally, themolecules of Formula One may also be used in combination (such as, in acompositional mixture, or a simultaneous or sequential application) withcompounds that are antifeedants, bird repellents, chemosterilants,herbicide safeners, insect attractants, insect repellents, mammalrepellents, mating disrupters, plant activators, plant growthregulators, or synergists. Examples of such compounds in the abovegroups that may be used with the Molecules of Formula Oneare—(3-ethoxypropyl)mercury bromide, 1,2-dichloropropane,1,3-dichloropropene, 1-methylcyclopropene, 1-naphthol,2-(octylthio)ethanol, 2,3,5-tri-iodobenzoic acid, 2,3,6-TBA,2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium,2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl,2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butometyl, 2,4,5-T-butotyl,2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl,2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium,2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D,2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl,2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium,2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl,2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium,2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl,2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl,2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl,2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium,2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium,2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP,2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP,4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA-sodium, 4-CPB, 4-CPP,4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate,8-phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate,acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole,acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl,acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein,acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor,alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin,allethrin, allicin, allidochlor, allosamidin, alloxydim,alloxydim-sodium, allyl alcohol, allyxycarb, alorac, alpha-cypermethrin,alpha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin,amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron,aminocarb, aminocyclopyrachlor, a minocyclopyrachlor-methyl,aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium,aminopyralid-tris(2-hydroxypropyl)ammonium, amiprofos-methyl,amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole,ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos,anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone,antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam,asulam-potassium, asulam-sodium, athidathion, atraton, atrazine,aureofungin, aviglycine, aviglycine hydrochloride, azaconazole,azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl,azinphos-methyl, aziprotryne, azithiram, azobenzene, azocyclotin,azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate,barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl,benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl,benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin,benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos,benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap,bentaluron, bentazone, bentazone-sodium, benthiavalicarb,benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox,benzadox-ammonium, benzalkonium chloride, benzamacril,benzamacril-isobutyl, benzamorf, benzfendizone, benzipram,benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid,benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzylbenzoate, benzyladenine, berberine, berberine chloride, beta-cyfluthrin,beta-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox,bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl,bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin,bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac,bispyribac-sodium, bistrifluron, bitertanol, bithionol, bixafen,blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid,brassinolide, brassinolide-ethyl, brevicomin, brodifacoum,brofenvalerate, brofluthrinate, bromacil, bromacil-lithium,bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos,bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT,bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil,bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxyniloctanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol,bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundymixture, busulfan, butacarb, butachlor, butafenacil, butamifos,butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron,butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin,butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos,cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide,calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor,captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam,carbendazim, carbendazim benzenesulfonate, carbendazim sulfite,carbetamide, carbofuran, carbon disulfide, carbon tetrachloride,carbophenothion, carbosulfan, carboxazole, carboxide, carboxin,carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartaphydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure,Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone,chlomethoxyfen, chloralose, chloramben, chloramben-ammonium,chloramben-diolamine, chloramben-methyl, chloramben-methylammonium,chloramben-sodium, chloramine phosphorus, chloramphenicol,chloraniformethan, chloranil, chloranocryl, chlorantraniliprole,chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside,chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane,chlordecone, chlordimeform, chlordimeform hydrochloride,chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac,chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole,chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide,chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren,chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon,chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequatchloride, chlornidine, chlornitrofen, chlorobenzilate,chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron,chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin,chloropon, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron,chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim,chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos,chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal,chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos,chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin II,cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide,cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop,clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium,clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone,clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl,clopyralid-olamine, clopyralid-potassium,clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet,cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel,clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA,codlelure, colophonate, copper acetate, copper acetoarsenite, copperarsenate, copper carbonate, basic, copper hydroxide, copper naphthenate,copper oleate, copper oxychloride, copper silicate, copper sulfate,copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl,coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol,crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure,cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide,cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate,cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide,cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin,cyclosulfamuron, cycloxaprid, cycloxydim, cycluron, cyenopyrafen,cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl,cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil,cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride,cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil,cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron,dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide,dayoutong, dazomet, dazomet-sodium, DBCP, d-camphor, DCIP, DCPTA, DDT,debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor,deltamethrin, demephion, demephion-O, demephion-S, demeton,demeton-methyl, demeton-O, demeton-O-methyl, demeton-S,demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn,d-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos,diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate,dicamba, dicamba-diglycolamine, dicamba-dimethylammonium,dicamba-diolamine, dicamba-isopropylammonium, dicamba-methyl,dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamine,dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone,dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl,dichlormate, dichlormid, dichlorophen, dichlorprop,dichlorprop-2-ethylhexyl, dichlorprop-butotyl,dichlorprop-dimethylammonium, dichlorprop-ethylammonium,dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P,dichlorprop-P-2-ethylhexyl, dichlorprop-P-dimethylammonium,dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline,diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine,diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl,dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat,diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb,dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum,difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron,difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin,diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium,diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin,dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb,dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin,dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate,dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon,dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole,diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6,dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinosebacetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium,dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate,dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion,diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone,diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquatdibromide, disparlure, disul, disulfiram, disulfoton, disul-sodium,ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron,d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium,dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicinhydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure,doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone,edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate,EMPC, empenthrin, endosulfan, endothal, endothal-diammonium,endothal-dipotassium, endothal-disodium, endothion, endrin,enestroburin, EPN, epocholeone, epofenonane, epoxiconazole,eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan,esdepallthrine, esfenvalerate, esprocarb, etacelasil, etaconazole,etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron,ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron,ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol,ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen,ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethylformate, ethyl α-naphthaleneacetate, ethyl-DDD, ethylene, ethylenedibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercurybromide, ethylmercury chloride, ethylmercury phosphate, etinofen,etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos,eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenamiphos,fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole,fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos,fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan,fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl,fenoprop-butometyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl,fenoprop-methyl, fenoprop-potassium, fenothiocarb, fenoxacrim,fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P,fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil,fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine,fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl,fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl,fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride,fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA,fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop,flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M-isopropyl,flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid,florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl,fluazifop-P, fluazifop-P-butyl, fluazinam, fluazolate, fluazuron,flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium,flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate,fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim,flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl,flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin,flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph,fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid,fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl,fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole,fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate,flupropanate-sodium, flupyradifurone, flupyrsulfuron,flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium, fluquinconazole,flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone,flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl,flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide,fluthiacet, fluthiacet-methyl, flutianil, flutolanil, flutriafol,fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen,fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde,formetanate, formetanate hydrochloride, formothion, formparanate,formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl,fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan,frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling,fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr,furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin,furfural, furilazole, furmecyclox, furophanate, furyloxyfen,gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellins,gliftor, glufosinate, glufosinate-ammonium, glufosinate-P,glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime,glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium,glyphosate-isopropylammonium, glyphosate-monoammonium,glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium,glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatineacetates, halacrinate, halfenprox, halofenozide, halosafen,halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop,haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl,haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD,heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone,hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole,hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos,hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo,hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide,hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil,imazalil nitrate, imazalil sulfate, imazamethabenz,imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic,imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin,imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr,imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos,imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate,iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan,indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane,iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium,iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil octanoate,ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone,iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol,IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos,isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin,isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane,isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron,isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl,isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos,japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid,jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan,jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenilehormone III, kadethrin, karbutilate, karetazan, karetazan-potassium,kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox,ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuicaoxi,lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil,lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure,looplure, lufenuron, Ivdingjunzhi, Ivxiancaolin, lythidathion, MAA,malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper,mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA,MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium,MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl,MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl,MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil,mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl,mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl,mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl,mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium,mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medimeform,medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr,mefenpyr-diethyl, mefluidide, mefluidide-diolamine,mefluidide-potassium, megatomoic acid, menazon, mepanipyrim,meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride,mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride,mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron,mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone,metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop,metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron,metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron,methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole,methfuroxam, methidathion, methiobencarb, methiocarb,methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos,methometon, methomyl, methoprene, methoprotryne, methoquin-butyl,methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methylapholate, methyl bromide, methyl eugenol, methyl iodide, methylisothiocyanate, methylacetophos, methylchloroform, methyldymron,methylene chloride, methylmercury benzoate, methylmercury dicyandiamide,methylmercury pentachlorophenoxide, methylneodecanamide, metiram,metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb,metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone,metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos,mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox,mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron,monochloroacetic acid, monocrotophos, monolinuron, monosulfuron,monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquatdichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid,moxidectin, MSMA, muscalure, myclobutanil, myclozolin,N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled,naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyaceticacids, naproanilide, napropamide, naptalam, naptalam-sodium, natamycin,neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine,nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin,nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl,norbormide, norflurazon, nornicotine, noruron, novaluron, noviflumuron,nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace,omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron,oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil,oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon,oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone,oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate,oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen,oxymatrine, oxytetracycline, oxytetracycline hydrochloride,paclobutrazol, paichongding, para-dichlorobenzene, parafluron, paraquat,paraquat dichloride, paraquat dimetilsulfate, parathion,parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid,penconazole, pencycuron, pendimethalin, penflufen, penfluron,penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin,pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazineoxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl,phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea,phenylmercury acetate, phenylmercury chloride, phenylmercury derivativeof pyrocatechol, phenylmercury nitrate, phenylmercury salicylate,phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl,phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb,phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram,picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl,picloram-olamine, picloram-potassium, picloram-triethylammonium,picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin,pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide,piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide,piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl,pirimiphos-methyl, plifenate, polycarbamate, polyoxins, polyoxorim,polyoxorim-zinc, polythialan, potassium arsenite, potassium azide,potassium cyanate, potassium gibberellate, potassium naphthenate,potassium polysulfide, potassium thiocyanate, potassiumα-naphthaleneacetate, pp′-DDT, prallethrin, precocene I, precocene II,precocene III, pretilachlor, primidophos, primisulfuron,primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese,proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol,profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl,prohexadione, prohexadione-calcium, prohydrojasmon, promacyl, promecarb,prometon, prometryn, promurit, propachlor, propamidine, propamidinedihydrochloride, propamocarb, propamocarb hydrochloride, propanil,propaphos, propaquizafop, propargite, proparthrin, propazine,propetamphos, propham, propiconazole, propineb, propisochlor, propoxur,propoxycarbazone, propoxycarbazone-sodium, propyl isome,propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin,prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarbhydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute,proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid,pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl,pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole,pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl,pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II,pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb,pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl,pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon,pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl,pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole,pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac-sodium, pyrolan,pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia,quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl,quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine,quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop,quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl,quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide,rebemide, resmethrin, rhodethanil, rhodojaponin-III, ribavirin,rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong,salicylanilide, sanguinarine, santonin, schradan, scilliroside,sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz,semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin,siduron, siglure, silafluofen, silatrane, silica gel, silthiofam,simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor,sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodiumfluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodiumorthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide,sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram,spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine,streptomycin, streptomycin sesquisulfate, strychnine, sulcatol,sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone,sulfiram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron,sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid,sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep,tau-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium,TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide,tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron,tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin,tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim,terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton,terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane,tetrachlorvinphos, tetraconazole, tetradifon, tetrafluron, tetramethrin,tetramethylfluthrin, tetramine, tetranactin, tetrasul, thallium sulfate,thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid,thiadifluor, thiamethoxam, thiapronil, thiazafluron, thiazopyr,thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone,thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl,thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam,thiocyclam hydrochloride, thiocyclam oxalate, thiodiazole-copper,thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal, thiometon,thionazin, thiophanate, thiophanate-methyl, thioquinox,thiosemicarbazide, thiosultap, thiosultap-diammonium,thiosultap-disodium, thiosultap-monosodium, thiotepa, thiram,thuringiensin, tiadinil, tiaojiean, tiocarbazil, tioclorim, tioxymid,tirpate, tolclofos-methyl, tolfenpyrad, tolylfluanid, tolylmercuryacetate, topramezone, tralkoxydim, tralocythrin, tralomethrin,tralopyril, transfluthrin, transpermethrin, tretamine, triacontanol,triadimefon, triadimenol, triafamone, tri-allate, triamiphos,triapenthenol, triarathene, triarimol, triasulfuron, triazamate,triazbutil, triaziflam, triazophos, triazoxide, tribenuron,tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide,trichlorfon, trichlormetaphos-3, trichloronat, triclopyr,triclopyr-butotyl, triclopyr-ethyl, triclopyr-triethylammonium,tricyclazole, tridemorph, tridiphane, trietazine, trifenmorph,trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium,triflumizole, triflumuron, trifluralin, triflusulfuron,triflusulfuron-methyl, trifop, trifop-methyl, trifopsime, triforine,trihydroxytriazine, trimedlure, trimethacarb, trimeturon, trinexapac,trinexapac-ethyl, triprene, tripropindan, triptolide, tritac,triticonazole, tritosulfuron, trunc-call, uniconazole, uniconazole-P,urbacide, uredepa, valerate, validamycin, valifenalate, valone,vamidothion, vangard, vaniliprole, vernolate, vinclozolin, warfarin,warfarin-potassium, warfarin-sodium, xiaochongliulin, xinjunan,xiwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing, zarilamid,zeatin, zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide,zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong,α-chlorohydrin, α-ecdysone, α-multistriatin, and α-naphthaleneaceticacid. For more information consult the “COMPENDIUM OF PESTICIDE COMMONNAMES” located at alanwood.net. Also consult “THE PESTICIDE MANUAL” 14thEdition, edited by C D S Tomlin, copyright 2006 by British CropProduction Council, or its prior or more recent editions.

Biopesticides

Molecules of Formula One may also be used in combination (such as in acompositional mixture, or a simultaneous or sequential application) withone or more biopesticides. The term “biopesticide” is used for microbialbiological pest control agents that are applied in a similar manner tochemical pesticides. Commonly these are bacterial, but there are alsoexamples of fungal control agents, including Trichoderma spp. andAmpelomyces quisqualis (a control agent for grape powdery mildew).Bacillus subtilis are used to control plant pathogens. Weeds and rodentshave also been controlled with microbial agents. One well-knowninsecticide example is Bacillus thuringiensis, a bacterial disease ofLepidoptera, Coleoptera, and Diptera. Because it has little effect onother organisms, it is considered more environmentally friendly thansynthetic pesticides. Biological insecticides include products based on:

1. entomopathogenic fungi (e.g. Metarhizium anisopliae);

2. entomopathogenic nematodes (e.g. Steinernema feltiae); and

3. entomopathogenic viruses (e.g. Cydia pomonella granulovirus).

Other examples of entomopathogenic organisms include, but are notlimited to, baculoviruses, bacteria and other prokaryotic organisms,fungi, protozoa and Microsproridia. Biologically derived insecticidesinclude, but not limited to, rotenone, veratridine, as well as microbialtoxins; insect tolerant or resistant plant varieties; and organismsmodified by recombinant DNA technology to either produce insecticides orto convey an insect resistant property to the genetically modifiedorganism. In one embodiment, the molecules of Formula One may be usedwith one or more biopesticides in the area of seed treatments and soilamendments. The Manual of Biocontrol Agents gives a review of theavailable biological insecticide (and other biology-based control)products. Copping L. G. (ed.) (2004). The Manual of Biocontrol Agents(formerly the Biopesticide Manual) 3rd Edition. British Crop ProductionCouncil (BCPC), Farnham, Surrey UK.

Other Active Compounds

Molecules of Formula One may also be used in combination (such as in acompositional mixture, or a simultaneous or sequential application) withone or more of the following:

-   1.    3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;-   2. 3-(4′-chloro-2,4-dimethyl    [1,1′-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;-   3. 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone;-   4.    4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone;-   5.    3-chloro-N2-[(1S)-1-methyl-2-(methylsulfonyl)ethyl]-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide;-   6. 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide;-   7. 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide;-   8. 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide;-   9. 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide;-   10. 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide;-   11. 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide;-   12. 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide;-   13.    3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-1-methyl-1H-pyrazole-4-carboxamide;-   14.    N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)    hydrazone;-   15.    N-ethyl-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)    hydrazone nicotine;-   16.    O-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1-(2-trifluoromethylphenyl)-vinyl]}    S-methyl thiocarbonate;-   17.    (E)-N1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1-methylacetamidine;-   18.    1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo[1,2-α]pyridin-5-ol;-   19. 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl    mesylate; and-   20.    N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)hydrazone.

Synergistic Mixtures

Molecules of Formula One may be used with certain active compounds toform synergistic mixtures where the mode of action of such compoundscompared to the mode of action of the molecules of Formula One are thesame, similar, or different. Examples of modes of action include, butare not limited to: acetylcholinesterase inhibitor; sodium channelmodulator; chitin biosynthesis inhibitor; GABA and glutamate-gatedchloride channel antagonist; GABA and glutamate-gated chloride channelagonist; acetylcholine receptor agonist; acetylcholine receptorantagonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinicacetylcholine receptor; Midgut membrane disrupter; oxidativephosphorylation disrupter, and ryanodine receptor (RyRs). Generally,weight ratios of the molecules of Formula One in a synergistic mixturewith another compound are from about 10:1 to about 1:10, in anotherembodiment from about 5:1 to about 1:5, and in another embodiment fromabout 3:1, and in another embodiment about 1:1.

Formulations

A pesticide is rarely suitable for application in its pure form. It isusually necessary to add other substances so that the pesticide can beused at the required concentration and in an appropriate form,permitting ease of application, handling, transportation, storage, andmaximum pesticide activity. Thus, pesticides are formulated into, forexample, baits, concentrated emulsions, dusts, emulsifiableconcentrates, fumigants, gels, granules, microencapsulations, seedtreatments, suspension concentrates, suspoemulsions, tablets, watersoluble liquids, water dispersible granules or dry flowables, wettablepowders, and ultra-low volume solutions. For further information onformulation types see “Catalogue of Pesticide Formulation Types andInternational Coding System” Technical Monograph n° 2, 5th Edition byCropLife International (2002).

Pesticides are applied most often as aqueous suspensions or emulsionsprepared from concentrated formulations of such pesticides. Suchwater-soluble, water-suspendable, or emulsifiable formulations areeither solids, usually known as wettable powders, or water dispersiblegranules, or liquids usually known as emulsifiable concentrates, oraqueous suspensions. Wettable powders, which may be compacted to formwater dispersible granules, comprise an intimate mixture of thepesticide, a carrier, and surfactants. The concentration of thepesticide is usually from about 10% to about 90% by weight. The carrieris usually selected from among the attapulgite clays, themontmorillonite clays, the diatomaceous earths, or the purifiedsilicates. Effective surfactants, comprising from about 0.5% to about10% of the wettable powder, are found among sulfonated lignins,condensed naphthalenesulfonates, naphthalenesulfonates,alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants suchas ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of pesticides comprise a convenientconcentration of a pesticide, such as from about 50 to about 500 gramsper liter of liquid dissolved in a carrier that is either a watermiscible solvent or a mixture of water-immiscible organic solvent andemulsifiers. Useful organic solvents include aromatics, especiallyxylenes and petroleum fractions, especially the high-boilingnaphthalenic and olefinic portions of petroleum such as heavy aromaticnaphtha. Other organic solvents may also be used, such as the terpenicsolvents including rosin derivatives, aliphatic ketones such ascyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitableemulsifiers for emulsifiable concentrates are selected from conventionalanionic and non-ionic surfactants.

Aqueous suspensions comprise suspensions of water-insoluble pesticidesdispersed in an aqueous carrier at a concentration in the range fromabout 5% to about 50% by weight. Suspensions are prepared by finelygrinding the pesticide and vigorously mixing it into a carrier comprisedof water and surfactants. Ingredients, such as inorganic salts andsynthetic or natural gums may also be added, to increase the density andviscosity of the aqueous carrier. It is often most effective to grindand mix the pesticide at the same time by preparing the aqueous mixtureand homogenizing it in an implement such as a sand mill, ball mill, orpiston-type homogenizer.

Pesticides may also be applied as granular compositions that areparticularly useful for applications to the soil. Granular compositionsusually contain from about 0.5% to about 10% by weight of the pesticide,dispersed in a carrier that comprises clay or a similar substance. Suchcompositions are usually prepared by dissolving the pesticide in asuitable solvent and applying it to a granular carrier which has beenpre-formed to the appropriate particle size, in the range of from about0.5 to about 3 mm. Such compositions may also be formulated by making adough or paste of the carrier and compound and crushing and drying toobtain the desired granular particle size.

Dusts containing a pesticide are prepared by intimately mixing thepesticide in powdered form with a suitable dusty agricultural carrier,such as kaolin clay, ground volcanic rock, and the like. Dusts cansuitably contain from about 1% to about 10% of the pesticide. They canbe applied as a seed dressing or as a foliage application with a dustblower machine.

It is equally practical to apply a pesticide in the form of a solutionin an appropriate organic solvent, usually petroleum oil, such as thespray oils, which are widely used in agricultural chemistry.

Pesticides can also be applied in the form of an aerosol composition. Insuch compositions the pesticide is dissolved or dispersed in a carrier,which is a pressure-generating propellant mixture. The aerosolcomposition is packaged in a container from which the mixture isdispensed through an atomizing valve.

Pesticide baits are formed when the pesticide is mixed with food or anattractant or both. When the pests eat the bait they also consume thepesticide. Baits may take the form of granules, gels, flowable powders,liquids, or solids. They can be used in pest harborages.

Fumigants are pesticides that have a relatively high vapor pressure andhence can exist as a gas in sufficient concentrations to kill pests insoil or enclosed spaces. The toxicity of the fumigant is proportional toits concentration and the exposure time. They are characterized by agood capacity for diffusion and act by penetrating the pest'srespiratory system or being absorbed through the pest's cuticle.Fumigants are applied to control stored product pests under gas proofsheets, in gas sealed rooms or buildings or in special chambers.

Pesticides can be microencapsulated by suspending the pesticideparticles or droplets in plastic polymers of various types. By alteringthe chemistry of the polymer or by changing factors in the processing,microcapsules can be formed of various sizes, solubility, wallthicknesses, and degrees of penetrability. These factors govern thespeed with which the active ingredient within is released, which inturn, affects the residual performance, speed of action, and odor of theproduct.

Oil solution concentrates are made by dissolving pesticide in a solventthat will hold the pesticide in solution. Oil solutions of a pesticideusually provide faster knockdown and kill of pests than otherformulations due to the solvents themselves having pesticidal action andthe dissolution of the waxy covering of the integument increasing thespeed of uptake of the pesticide. Other advantages of oil solutionsinclude better storage stability, better penetration of crevices, andbetter adhesion to greasy surfaces.

Another embodiment is an oil-in-water emulsion, wherein the emulsioncomprises oily globules which are each provided with a lamellar liquidcrystal coating and are dispersed in an aqueous phase, wherein each oilyglobule comprises at least one compound which is agriculturally active,and is individually coated with a monolamellar or oligolamellar layercomprising: (1) at least one non-ionic lipophilic surface-active agent,(2) at least one non-ionic hydrophilic surface-active agent and (3) atleast one ionic surface-active agent, wherein the globules having a meanparticle diameter of less than 800 nanometers. Further information onthe embodiment is disclosed in U.S. patent publication 20070027034published Feb. 1, 2007, having patent application Ser. No. 11/495,228.For ease of use, this embodiment will be referred to as “OIWE”.

For further information consult “Insect Pest Management” 2nd Edition byD. Dent, copyright CAB International (2000). Additionally, for moredetailed information consult “Handbook of Pest Control—The Behavior,Life History, and Control of Household Pests” by Arnold Mallis, 9thEdition, copyright 2004 by GIE Media Inc.

Other Formulation Components

Generally, when the molecules disclosed in Formula One are used in aformulation, such formulation can also contain other components. Thesecomponents include, but are not limited to, (this is a non-exhaustiveand non-mutually exclusive list) wetters, spreaders, stickers,penetrants, buffers, sequestering agents, drift reduction agents,compatibility agents, anti-foam agents, cleaning agents, andemulsifiers. A few components are described forthwith.

A wetting agent is a substance that when added to a liquid increases thespreading or penetration power of the liquid by reducing the interfacialtension between the liquid and the surface on which it is spreading.Wetting agents are used for two main functions in agrochemicalformulations: during processing and manufacture to increase the rate ofwetting of powders in water to make concentrates for soluble liquids orsuspension concentrates; and during mixing of a product with water in aspray tank to reduce the wetting time of wettable powders and to improvethe penetration of water into water-dispersible granules. Examples ofwetting agents used in wettable powder, suspension concentrate, andwater-dispersible granule formulations are: sodium lauryl sulfate;sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphaticalcohol ethoxylates.

A dispersing agent is a substance which adsorbs onto the surface ofparticles and helps to preserve the state of dispersion of the particlesand prevents them from reaggregating. Dispersing agents are added toagrochemical formulations to facilitate dispersion and suspension duringmanufacture, and to ensure the particles redisperse into water in aspray tank. They are widely used in wettable powders, suspensionconcentrates and water-dispersible granules. Surfactants that are usedas dispersing agents have the ability to adsorb strongly onto a particlesurface and provide a charged or steric barrier to reaggregation ofparticles. The most commonly used surfactants are anionic, non-ionic, ormixtures of the two types. For wettable powder formulations, the mostcommon dispersing agents are sodium lignosulfonates. For suspensionconcentrates, very good adsorption and stabilization are obtained usingpolyelectrolytes, such as sodium naphthalene sulfonate formaldehydecondensates. Tristyrylphenol ethoxylate phosphate esters are also used.Non-ionics such as alkylarylethylene oxide condensates and EO-PO blockcopolymers are sometimes combined with anionics as dispersing agents forsuspension concentrates. In recent years, new types of very highmolecular weight polymeric surfactants have been developed as dispersingagents. These have very long hydrophobic ‘backbones’ and a large numberof ethylene oxide chains forming the ‘teeth’ of a ‘comb’ surfactant.These high molecular weight polymers can give very good long-termstability to suspension concentrates because the hydrophobic backboneshave many anchoring points onto the particle surfaces. Examples ofdispersing agents used in agrochemical formulations are: sodiumlignosulfonates; sodium naphthalene sulfonate formaldehyde condensates;tristyrylphenol ethoxylate phosphate esters; aliphatic alcoholethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graftcopolymers.

An emulsifying agent is a substance which stabilizes a suspension ofdroplets of one liquid phase in another liquid phase. Without theemulsifying agent the two liquids would separate into two immiscibleliquid phases. The most commonly used emulsifier blends containalkylphenol or aliphatic alcohol with twelve or more ethylene oxideunits and the oil-soluble calcium salt of dodecylbenzenesulfonic acid. Arange of hydrophile-lipophile balance (“HLB”) values from 8 to 18 willnormally provide good stable emulsions. Emulsion stability can sometimesbe improved by the addition of a small amount of an EO-PO blockcopolymer surfactant.

A solubilizing agent is a surfactant which will form micelles in waterat concentrations above the critical micelle concentration. The micellesare then able to dissolve or solubilize water-insoluble materials insidethe hydrophobic part of the micelle. The types of surfactants usuallyused for solubilization are non-ionics, sorbitan monooleates, sorbitanmonooleate ethoxylates, and methyl oleate esters.

Surfactants are sometimes used, either alone or with other additivessuch as mineral or vegetable oils as adjuvants to spray-tank mixes toimprove the biological performance of the pesticide on the target. Thetypes of surfactants used for bioenhancement depend generally on thenature and mode of action of the pesticide. However, they are oftennon-ionics such as: alkyl ethoxylates; linear aliphatic alcoholethoxylates; aliphatic amine ethoxylates.

A carrier or diluent in an agricultural formulation is a material addedto the pesticide to give a product of the required strength. Carriersare usually materials with high absorptive capacities, while diluentsare usually materials with low absorptive capacities. Carriers anddiluents are used in the formulation of dusts, wettable powders,granules and water-dispersible granules.

Organic solvents are used mainly in the formulation of emulsifiableconcentrates, oil-in-water emulsions, suspoemulsions, and ultra-lowvolume formulations, and to a lesser extent, granular formulations.Sometimes mixtures of solvents are used. The first main groups ofsolvents are aliphatic paraffinic oils such as kerosene or refinedparaffins. The second main group (and the most common) comprises thearomatic solvents such as xylene and higher molecular weight fractionsof C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful ascosolvents to prevent crystallization of pesticides when the formulationis emulsified into water. Alcohols are sometimes used as cosolvents toincrease solvent power. Other solvents may include vegetable oils, seedoils, and esters of vegetable and seed oils.

Thickeners or gelling agents are used mainly in the formulation ofsuspension concentrates, emulsions and suspoemulsions to modify therheology or flow properties of the liquid and to prevent separation andsettling of the dispersed particles or droplets. Thickening, gelling,and anti-settling agents generally fall into two categories, namelywater-insoluble particulates and water-soluble polymers. It is possibleto produce suspension concentrate formulations using clays and silicas.Examples of these types of materials, include, but are not limited to,montmorillonite, bentonite, magnesium aluminum silicate, andattapulgite. Water-soluble polysaccharides have been used asthickening-gelling agents for many years. The types of polysaccharidesmost commonly used are natural extracts of seeds and seaweeds or aresynthetic derivatives of cellulose. Examples of these types of materialsinclude, but are not limited to, guar gum; locust bean gum; carrageenam;alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC);hydroxyethyl cellulose (HEC). Other types of anti-settling agents arebased on modified starches, polyacrylates, polyvinyl alcohol andpolyethylene oxide. Another good anti-settling agent is xanthan gum.

Microorganisms can cause spoilage of formulated products. Thereforepreservation agents are used to eliminate or reduce their effect.Examples of such agents include, but are not limited to: propionic acidand its sodium salt; sorbic acid and its sodium or potassium salts;benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt;methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).

The presence of surfactants often causes water-based formulations tofoam during mixing operations in production and in application through aspray tank. In order to reduce the tendency to foam, anti-foam agentsare often added either during the production stage or before fillinginto bottles. Generally, there are two types of anti-foam agents, namelysilicones and non-silicones. Silicones are usually aqueous emulsions ofdimethyl polysiloxane, while the non-silicone anti-foam agents arewater-insoluble oils, such as octanol and nonanol, or silica. In bothcases, the function of the anti-foam agent is to displace the surfactantfrom the air-water interface.

“Green” agents (e.g., adjuvants, surfactants, solvents) can reduce theoverall environmental footprint of crop protection formulations. Greenagents are biodegradable and generally derived from natural and/orsustainable sources, e.g. plant and animal sources. Specific examplesare: vegetable oils, seed oils, and esters thereof, also alkoxylatedalkyl polyglucosides.

For further information, see “Chemistry and Technology of AgrochemicalFormulations” edited by D. A. Knowles, copyright 1998 by Kluwer AcademicPublishers. Also see “Insecticides in Agriculture andEnvironment—Retrospects and Prospects” by A. S. Perry, I. Yamamoto, I.Ishaaya, and R. Perry, copyright 1998 by Springer-Verlag.

Pests

In general, the molecules of Formula One may be used to control pestse.g. beetles, earwigs, cockroaches, flies. aphids, scales, whiteflies,leafhoppers, ants, wasps, termites, moths, butterflies, lice,grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites,ticks, nematodes, and symphylans.

In another embodiment, the molecules of Formula One may be used tocontrol pests in the Phyla Nematoda and/or Arthropoda.

In another embodiment, the molecules of Formula One may be used tocontrol pests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.

In another embodiment, the molecules of Formula One may be used tocontrol pests in the Classes of Arachnida, Symphyla, and/or Insecta.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Anoplura. A non-exhaustive list of particulargenera includes, but is not limited to, Haematopinus spp., Hoplopleuraspp., Linognathus spp., Pediculus spp., and Polyp/ax spp. Anon-exhaustive list of particular species includes, but is not limitedto, Haematopinus asini, Haematopinus suis, Linognathus setosus,Linognathus ovillus, Pediculus humanus capitis, Pediculus humanushumanus, and Pthirus pubis.

In another embodiment, the molecules of Formula One may be used tocontrol pests in the Order Coleoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Acanthoscelides spp.,Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophoraspp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp.,Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp.,Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp.,Megascelis spp., Meligethes spp., Otiorhynchus spp., Pantomorus spp.,Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp.,Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp.,and Tribolium spp. A non-exhaustive list of particular species includes,but is not limited to, Acanthoscelides obtectus, Agrilus planipennis,Anoplophora glabripennis, Anthonomus grandis, Ataenius spretulus,Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum,Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata,Cerotoma trifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi,Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinisnitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestespusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporausmarginatus, Dermestes lardarius, Dermestes maculatus, Epilachnavarivestis, Faustinus cubae, Hylobius pales, Hypera postica,Hypothenemus hampei, Lasioderma serricorne, Leptinotarsa decemlineata,Liogenys fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus,Maecolaspis joliveti, Melanotus communis, Meligethes aeneus, Melolonthamelolontha, Oberea brevis, Oberea linearis, Oryctes rhinoceros,Oryzaephilus mercator, Oryzaephilus surinamensis, Oulema melanopus,Oulema oryzae, Phyllophaga cuyabana, Popillia japonica, Prostephanustruncatus, Rhyzopertha dominica, Sitona lineatus, Sitophilus granarius,Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum, Triboliumcastaneum, Tribolium confusum, Trogoderma variabile, and Zabrustenebrioides.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Dermaptera.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Blattaria. A non-exhaustive list ofparticular species includes, but is not limited to, Blattella germanica,Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana,Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa,Pycnoscelus surinamensis, and Supella longipalpa.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Diptera. A non-exhaustive list of particulargenera includes, but is not limited to, Aedes spp., Agromyza spp.,Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp.,Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp., Dasineuraspp., Delia spp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyzaspp., Musca spp., Phorbia spp., Tabanus spp., and Tipula spp. Anon-exhaustive list of particular species includes, but is not limitedto, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens,Anastrepha obliqa, Bactrocera cucurbitae, Bactrocera dorsalis,Bactrocera invadens, Bactrocera zonata, Ceratitis capitata, Dasineurabrassicae, Delia platura, Fannia canicularis, Fannia scalaris,Gasterophilus intestinalis, Gracillia perseae, Haematobia irritans,Hypoderma lineatum, Liriomyza brassicae, Melophagus ovinus, Muscaautumnalis, Musca domestica, Oestrus ovis, Oscinella frit, Pegomyabetae, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletismendax, Sitodiplosis mosellana, and Stomoxys calcitrans.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Hemiptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Adelges spp.,Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastesspp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp.,Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp.,Nephotettix spp., Nezara spp., Philaenus spp., Phytocoris spp.,Piezodorus spp., Planococcus spp., Pseudococcus spp., Rhopalosiphumspp., Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp.,Trialeurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive listof particular species includes, but is not limited to, Acrosternumhilare, Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicusdispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula,Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphis pomi,Aulacorthum solani, Bemisia argentifolii, Bemisia tabaci, Blissusleucopterus, Brachycorynella asparagi, Brevennia rehi, Brevicorynebrassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex hemipterus,Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus, Diuraphisnoxia, Diaphorina citri, Dysaphis plantaginea, Dysdercus suturellus,Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura, Euschistusheros, Euschistus servus, Helopeltis antonii, Helopeltis theivora,Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus,Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus,Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarium,Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarva frimbiolata,Metopolophium dirhodum, Mictis longicornis, Myzus persicae, Nephotettixcinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvatalugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis,Phylloxera vitifoliae, Physokermes piceae, Phytocoris californicus,Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus,Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes,Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi,Saissetia oleae, Scaptocoris castanea, Schizaphis graminum, Sitobionavenae, Sogatella furcifera, Trialeurodes vaporariorum, Trialeurodesabutiloneus, Unaspis yanonensis, and Zulia entrerriana.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Hymenoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Acromyrmex spp., Attaspp., Camponotus spp., Diprion spp., Formica spp., Monomorium spp.,Neodiprion spp., Pogonomyrmex spp., Polistes spp., Solenopsis spp.,Vespula spp., and Xylocopa spp. A non-exhaustive list of particularspecies includes, but is not limited to, Athalia rosae, Atta texana,Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis,Solenopsis invicta, Solenopsis geminata, Solenopsis molesta, Solenopsisrichtery, Solenopsis xyloni, and Tapinoma sessile.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Isoptera. A non-exhaustive list of particulargenera includes, but is not limited to, Coptotermes spp., Cornitermesspp., Cryptotermes spp., Heterotermes spp., Kalotermes spp.,Incisitermes spp., Macrotermes spp., Marginitermes spp., Microcerotermesspp., Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp.,and Zootermopsis spp. A non-exhaustive list of particular speciesincludes, but is not limited to, Coptotermes curvignathus, Coptotermesfrenchi, Coptotermes formosanus, Heterotermes aureus, Microtermes obesi,Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermesflavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermessantonensis, Reticulitermes speratus, Reticulitermes tibialis, andReticulitermes virginicus.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Lepidoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Adoxophyes spp.,Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilospp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp.,Diatraea spp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp.,Gortyna spp., Helicoverpa spp., Heliothis spp., Indarbela spp.,Lithocolletis spp., Loxagrotis spp., Malacosoma spp., Peridroma spp.,Phyllonorycter spp., Pseudaletia spp., Sesamia spp., Spodoptera spp.,Synanthedon spp., and Yponomeuta spp. A non-exhaustive list ofparticular species includes, but is not limited to, Achaea janata,Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana,Amyelois transitella, Anacamptodes defectaria, Anarsia lineatella,Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archipsrosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes,Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposinaniponensis, Chilo suppressalis, Chilo polychrysus, Chlumetia transversa,Choristoneura rosaceana, Cnaphalocrocis medinalis, Conopomorphacramerella, Cossus cossus, Cydia caryana, Cydia funebrana, Cydiamolesta, Cydia nigricana, Cydia pomonella, Darna diducta, Diatraeasaccharalis, Diatraea grandiosella, Earias insulana, Earias vittella,Ecdytolopha aurantianum, Elasmopalpus lignosellus, Ephestia cautella,Ephestia elutella, Ephestia kuehniella, Epinotia aporema, Epiphyaspostvittana, Erionota thrax, Eupoecilia ambiguella, Euxoa auxiliaris,Grapholita molesta, Hedylepta indicata, Helicoverpa armigera,Helicoverpa zea, Heliothis virescens, Hellula undalis, Keiferialycopersicella, Leucinodes orbonalis, Leucoptera coffeella, Leucopteramalifoliella, Lobesia botrana, Loxagrotis albicosta, Lymantria dispar,Lyonetia clerkella, Mahasena corbetti, Mamestra brassicae, Marucatestulalis, Metisa plana, Mythimna unipuncta, Neoleucinodes elegantalis,Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydiavesulia, Pandemis cerasana, Pandemis heparana, Papilio demodocus,Pectinophora gossypiella, Peridroma saucia, Perileucoptera coffeella,Phthorimaea operculella, Phyllocnistis citrella, Pieris rapae,Plathypena scabra, Plodia interpunctella, Plutella xylostella,Polychrosis viteana, Prays endocarpa, Prays o/leae, Pseudaletiaunipuncta, Pseudoplusia includens, Rachiplusia nu, Scirpophagaincertulas, Sesamia inferens, Sesamia nonagrioides, Setora nitens,Sitotroga cerealella, Sparganothis pilleriana, Spodoptera exigua,Spodoptera frugiperda, Spodoptera eridania, Thecla basilides, Tineolabisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae, andZeuzera pyrina.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Mallophaga. A non-exhaustive list ofparticular genera includes, but is not limited to, Anaticola spp.,Bovicola spp., Chelopistes spp., Goniodes spp., Menacanthus spp., andTrichodectes spp. A non-exhaustive list of particular species includes,but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis,Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas,Menacanthus stramineus, Menopon gallinae, and Trichodectes canis.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Orthoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Melanoplus spp., andPterophylla spp. A non-exhaustive list of particular species includes,but is not limited to, Anabrus simplex, Gryllotalpa africana,Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla,Locusta migratoria, Microcentrum retinerve, Schistocerca gregaria, andScudderia furcata.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Siphonaptera. A non-exhaustive list ofparticular species includes, but is not limited to, Ceratophyllusgallinae, Ceratophyllus niger, Ctenocephalides canis, Ctenocephalidesfelis, and Pulex irritans.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Thysanoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Caliothrips spp.,Frankliniella spp., Scirtothrips spp., and Thrips spp. A non-exhaustivelist of particular sp. includes, but is not limited to, Frankliniellafusca, Frankliniella occidentalis, Frankliniella schultzei,Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothripscruentatus, Scirtothrips citri, Scirtothrips dorsalis, and Taeniothripsrhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thripsorientalis, Thrips tabaci.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Thysanura. A non-exhaustive list ofparticular genera includes, but is not limited to, Lepisma spp. andThermobia spp.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Acarina. A non-exhaustive list of particulargenera includes, but is not limited to, Acarus spp., Aculops spp.,Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp.,Eriophyes spp., Ixodes spp., Oligonychus spp., Panonychus spp.,Rhizoglyphus spp., and Tetranychus spp. A non-exhaustive list ofparticular species includes, but is not limited to, Acarapis woodi,Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi,Aculus schlechtendali, Amblyomma americanum, Brevipalpus obovatus,Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoidespteronyssinus, Eotetranychus carpini, Notoedres cati, Oligonychuscoffeae, Oligonychus ilicis, Panonychus citri, Panonychus ulmi,Phyllocoptruta oleivora, Polyphagotarsonemus latus, Rhipicephalussanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychusurticae, and Varroa destructor.

In another embodiment, the molecules of Formula One may be used tocontrol pest of the Order Symphyla. A non-exhaustive list of particularsp. includes, but is not limited to, Scutigerella immaculata.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Phylum Nematoda. A non-exhaustive list ofparticular genera includes, but is not limited to, Aphelenchoides spp.,Belonolaimus spp., Criconemella spp., Ditylenchus spp., Heterodera spp.,Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchusspp., and Radopholus spp. A non-exhaustive list of particular sp.includes, but is not limited to, Dirofilaria immitis, Heterodera zeae,Meloidogyne incognita, Meloidogyne javanica, Onchocerca volvulus,Radopholus similis, and Rotylenchulus reniformis.

For additional information consult “HANDBOOK OF PEST CONTROL—THEBEHAVIOR, LIFE HISTORY, AND CONTROL OF HOUSEHOLD PESTS” by ArnoldMallis, 9th Edition, copyright 2004 by GIE Media Inc.

Applications

Molecules of Formula One are generally used in amounts from about 0.01grams per hectare to about 5000 grams per hectare to provide control.Amounts from about 0.1 grams per hectare to about 500 grams per hectareare generally preferred, and amounts from about 1 gram per hectare toabout 50 grams per hectare are generally more preferred.

The area to which a molecule of Formula One is applied can be any areainhabited (or maybe inhabited, or traversed by) a pest, for example:where crops, trees, fruits, cereals, fodder species, vines, turf andornamental plants, are growing; where domesticated animals are residing;the interior or exterior surfaces of buildings (such as places wheregrains are stored), the materials of construction used in building (suchas impregnated wood), and the soil around buildings. Particular cropareas to use a molecule of Formula One include areas where apples, corn,sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley,oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes,peppers, crucifers, pears, tobacco, almonds, sugar beets, beans andother valuable crops are growing or the seeds thereof are going to beplanted. It is also advantageous to use ammonium sulfate with a moleculeof Formula One when growing various plants.

Controlling pests generally means that pest populations, pest activity,or both, are reduced in an area. This can come about when: pestpopulations are repulsed from an area; when pests are incapacitated inor around an area; or pests are exterminated, in whole, or in part, inor around an area. Of course, a combination of these results can occur.Generally, pest populations, activity, or both are desirably reducedmore than fifty percent, preferably more than 90 percent. Generally, thearea is not in or on a human; consequently, the locus is generally anon-human area.

The molecules of Formula One may be used in mixtures, appliedsimultaneously or sequentially, alone or with other compounds to enhanceplant vigor (e.g. to grow a better root system, to better withstandstressful growing conditions). Such other compounds are, for example,compounds that modulate plant ethylene receptors, most notably1-methylcyclopropene (also known as 1-MCP). Furthermore, such moleculesmay be used during times when pest activity is low, such as before theplants that are growing begin to produce valuable agriculturalcommodities. Such times include the early planting season when pestpressure is usually low.

The molecules of Formula One can be applied to the foliar and fruitingportions of plants to control pests. The molecules will either come indirect contact with the pest, or the pest will consume the pesticidewhen eating leaf, fruit mass, or extracting sap, that contains thepesticide. The molecules of Formula One can also be applied to the soil,and when applied in this manner, root and stem feeding pests can becontrolled. The roots can absorb a molecule taking it up into the foliarportions of the plant to control above ground chewing and sap feedingpests.

Generally, with baits, the baits are placed in the ground where, forexample, termites can come into contact with, and/or be attracted to,the bait. Baits can also be applied to a surface of a building,(horizontal, vertical, or slant surface) where, for example, ants,termites, cockroaches, and flies, can come into contact with, and/or beattracted to, the bait. Baits can comprise a molecule of Formula One.

The molecules of Formula One can be encapsulated inside, or placed onthe surface of a capsule. The size of the capsules can range fromnanometer size (about 100-900 nanometers in diameter) to micrometer size(about 10-900 microns in diameter).

Because of the unique ability of the eggs of some pests to resistcertain pesticides, repeated applications of the molecules of FormulaOne may be desirable to control newly emerged larvae.

Systemic movement of pesticides in plants may be utilized to controlpests on one portion of the plant by applying (for example by sprayingan area) the molecules of Formula One to a different portion of theplant. For example, control of foliar-feeding insects can be achieved bydrip irrigation or furrow application, by treating the soil with forexample pre- or post-planting soil drench, or by treating the seeds of aplant before planting.

Seed treatment can be applied to all types of seeds, including thosefrom which plants genetically modified to express specialized traitswill germinate. Representative examples include those expressingproteins toxic to invertebrate pests, such as Bacillus thuringiensis orother insecticidal toxins, those expressing herbicide resistance, suchas “Roundup Ready” seed, or those with “stacked” foreign genesexpressing insecticidal toxins, herbicide resistance,nutrition-enhancement, drought resistance, or any other beneficialtraits. Furthermore, such seed treatments with the molecules of FormulaOne may further enhance the ability of a plant to better withstandstressful growing conditions. This results in a healthier, more vigorousplant, which can lead to higher yields at harvest time. Generally, about1 gram of the molecules of Formula One to about 500 grams per 100,000seeds is expected to provide good benefits, amounts from about 10 gramsto about 100 grams per 100,000 seeds is expected to provide betterbenefits, and amounts from about 25 grams to about 75 grams per 100,000seeds is expected to provide even better benefits.

It should be readily apparent that the molecules of Formula One may beused on, in, or around plants genetically modified to expressspecialized traits, such as Bacillus thuringiensis or other insecticidaltoxins, or those expressing herbicide resistance, or those with“stacked” foreign genes expressing insecticidal toxins, herbicideresistance, nutrition-enhancement, or any other beneficial traits.

The molecules of Formula One may be used for controlling endoparasitesand ectoparasites in the veterinary medicine sector or in the field ofnon-human animal keeping. The molecules of Formula One are applied, suchas by oral administration in the form of, for example, tablets,capsules, drinks, granules, by dermal application in the form of, forexample, dipping, spraying, pouring on, spotting on, and dusting, and byparenteral administration in the form of, for example, an injection.

The molecules of Formula One may also be employed advantageously inlivestock keeping, for example, cattle, sheep, pigs, chickens, andgeese. They may also be employed advantageously in pets such as, horses,dogs, and cats. Particular pests to control would be fleas and ticksthat are bothersome to such animals. Suitable formulations areadministered orally to the animals with the drinking water or feed. Thedosages and formulations that are suitable depend on the species.

The molecules of Formula One may also be used for controlling parasiticworms, especially of the intestine, in the animals listed above.

The molecules of Formula One may also be employed in therapeutic methodsfor human health care. Such methods include, but are limited to, oraladministration in the form of, for example, tablets, capsules, drinks,granules, and by dermal application.

Pests around the world have been migrating to new environments (for suchpest) and thereafter becoming a new invasive species in such newenvironment. The molecules of Formula One may also be used on such newinvasive species to control them in such new environment.

The molecules of Formula One may also be used in an area where plants,such as crops, are growing (e.g. pre-planting, planting, pre-harvesting)and where there are low levels (even no actual presence) of pests thatcan commercially damage such plants. The use of such molecules in sucharea is to benefit the plants being grown in the area. Such benefits,may include, but are not limited to, improving the health of a plant,improving the yield of a plant (e.g. increased biomass and/or increasedcontent of valuable ingredients), improving the vigor of a plant (e.g.improved plant growth and/or greener leaves), improving the quality of aplant (e.g. improved content or composition of certain ingredients), andimproving the tolerance to abiotic and/or biotic stress of the plant.

Before a pesticide can be used or sold commercially, such pesticideundergoes lengthy evaluation processes by various governmentalauthorities (local, regional, state, national, and international).Voluminous data requirements are specified by regulatory authorities andmust be addressed through data generation and submission by the productregistrant or by a third party on the product registrant's behalf, oftenusing a computer with a connection to the World Wide Web. Thesegovernmental authorities then review such data and if a determination ofsafety is concluded, provide the potential user or seller with productregistration approval. Thereafter, in that locality where the productregistration is granted and supported, such user or seller may use orsell such pesticide.

A molecule according to Formula One can be tested to determine itsefficacy against pests. Furthermore, mode of action studies can beconducted to determine if said molecule has a different mode of actionthan other pesticides. Thereafter, such acquired data can bedisseminated, such as by the internet, to third parties.

The headings in this document are for convenience only and must not beused to interpret any portion hereof.

Table Section

TABLE 2 Structure and Preparation Method for F Series Compounds Prep.according to No. Structure example F1

18 F2

18 F3

17 F4

17 F5

17 F6

17 F7

17 F8

17 F9

20 F10

20 F11

20 F12

18 F13

18 F14

19 F15

19 F16

19 F17

19 F18

19 F19

18 F20

23 F21

25 F22

28 F23

28

TABLE 3 Analytical Data for Compounds in Table 2 Mass No. (m/z) ¹H NMR¹⁹F NMR F1 ESIMS ¹H NMR (400 MHz, CDCl₃) δ ¹⁹F NMR (376 MHz, m/z 6437.79-7.69 (m, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.55 (d, CDCl₃) δ ([M −H]⁻) J = 5.4 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), −59.34, −66.97, 7.40 (s,2H), 7.34 (d, J = 7.9 Hz, 1H), −68.61. 6.55 (dd, J = 16.0, 4.5 Hz, 1H),6.39 (ddd, J = 15.9, 8.0, 2.6 Hz, 1H), 5.64 (h, J = 7.5 Hz, 1H), 4.10(pd, J = 8.7, 3.0 Hz, 1H), 2.44-2.00 (m, 4H), 1.51 (d, J = 6.7 Hz, 3H)F2 ESIMS ¹H NMR (400 MHz, CDCl₃) δ 8.27 (d, J = 17.8 Hz, ¹⁹F NMR (376MHz, m/z 629 2H), 7.43-7.33 (m, 3H), 7.28 (d, CDCl₃) δ ([M − H]⁻) J =8.3 Hz, 1H), 7.17 (dd, J = 7.8, 3.2 Hz, −59.63, −63.29, 1H), 6.53-6.43(m, 1H), 6.33 (ddd, J = 15.9, −68.60 8.0, 5.0 Hz, 1H), 5.89 (dq, J =13.8, 6.2 Hz, 1H), 4.07 (hept, J = 8.3 Hz, 1H), 3.04 (p, J = 11.2 Hz,1H), 2.87 (p, J = 10.5 Hz, 1H), 1.41 (d, J = 6.4 Hz, 3H) F3 ESIMS ¹H NMR(400 MHz, CDCl₃) δ ¹⁹F NMR (376 MHz, m/z 617 7.69-7.63 (m, 1H), 7.57(dd, J = 8.0, 1.7 Hz, 1H), CDCl₃) δ ([M − H]⁻) 7.47 (d, J = 8.0 Hz, 1H),7.41 (s, 2H), −59.06, −68.57 6.91 (d, J = 7.4 Hz, 1H), 6.66-6.55 (m,2H), 6.42 (dd, J = 15.9, 7.8 Hz, 1H), 5.42 (h, J = 7.0 Hz, 1H), 4.12 (p,J = 8.4 Hz, 1H), 2.16 (dd, J = 8.3, 6.9 Hz, 2H), 1.68 (d, J = 6.7 Hz,3H), 1.62 (q, J = 7.5 Hz, 2H), 1.38-1.22 (m, 4H), 0.93-0.85 (m, 3H) F4ESIMS ¹H NMR (400 MHz, CDCl₃) δ 7.68 (d, J = 12.0 Hz, ¹⁹F NMR (376 MHz,m/z 617 1H), 7.64-7.54 (m, 1H), DMSO- ([M − H]⁻) 7.47 (d, J = 7.9 Hz,1H), 7.41 (s, 2H), 6.86 (d, d₆) δ −57.81, −67.95 J = 7.4 Hz, 1H), 6.62(dd, J = 15.9, 7.5 Hz, 1H), 6.55 (d, J = 7.6 Hz, 1H), 6.43 (dd, J =15.9, 7.9 Hz, 1H), 5.42 (q, J = 7.2 Hz, 1H), 4.12 (p, J = 8.5 Hz, 1H),2.22-2.13 (m, 2H), 1.69 (d, J = 6.8 Hz, 3H), 1.63-1.41 (m, 3H), 0.90 (d,J = 6.4 Hz, 6H) F5 ESIMS ¹H NMR (400 MHz, CDCl₃) δ 7.66 (s, 1H), ¹⁹F NMR(376 MHz, m/z 603 7.57 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 27.1 Hz, DMSO-([M − H]⁻) 3H), 6.85 (d, J = 7.3 Hz, 1H), d₆) δ −57.81, −67.95 6.66-6.50(m, 2H), 6.43 (dd, J = 15.9, 7.8 Hz, 1H), 5.42 (q, J = 7.2 Hz, 1H), 4.12(p, J = 8.6 Hz, 1H), 2.22-2.13 (m, 2H), 1.69 (d, J = 6.8 Hz, 3H),1.64-1.55 (m, 2H), 1.42-1.23 (m, 2H), 0.92 (t, J = 7.3 Hz, 3H) F6 ESIMS¹H NMR (400 MHz, CDCl₃) δ 7.66 (d, J = 1.5 Hz, ¹⁹F NMR (376 MHz, m/z 6031H), 7.57 (d, J = 7.9 Hz, 1H), DMSO- ([M − H]⁻) 7.47 (d, J = 8.0 Hz,1H), 7.41 (s, 2H), 6.88 (d, d₆) δ −57.81, −67.95 J = 7.4 Hz, 1H), 6.61(d, J = 15.9 Hz, 1H), 6.54 (d, J = 7.6 Hz, 1H), 6.43 (dd, J = 15.9, 7.8Hz, 1H), 5.44 (p, J = 7.0 Hz, 1H), 4.12 (p, J = 8.6 Hz, 1H), 2.17-2.00(m, 2H), 1.69 (d, J = 6.8 Hz, 3H), 0.95 (d, J = 6.2 Hz, 7H) F7 ESIMS ¹HNMR (400 MHz, CDCl₃) δ 7.66 (d, J = 1.6 Hz, ¹⁹F NMR (376 MHz, m/z 5891H), 7.57 (dd, J = 8.0, 1.7 Hz, CDCl₃) δ ([M + H]⁺) 1H), 7.47 (d, J =8.0 Hz, 1H), 7.41 (s, 2H), −59.06, −68.57 6.92 (d, J = 7.4 Hz, 1H), 6.79(d, J = 7.6 Hz, 1H), 6.61 (d, J = 15.9 Hz, 1H), 6.42 (dd, J = 15.9, 7.8Hz, 1H), 5.43 (h, J = 6.9 Hz, 1H), 4.12 (p, J = 8.5 Hz, 1H), 1.69 (d, J= 6.8 Hz, 3H), 1.36 (tt, J = 7.8, 4.5 Hz, 1H), 0.93 (dt, J = 4.6, 3.2Hz, 2H), 0.77 (dt, J = 7.9, 3.4 Hz, 2H) F8 ESIMS ¹H NMR (400 MHz, CDCl₃)δ ¹⁹F NMR (376 MHz, m/z 603 7.72-7.63 (m, 1H), 7.63-7.52 (m, 1H), 7.48(d, J = 7.9 Hz, CDCl₃) δ ([M + H]⁺) 1H), 7.41 (d, J = 1.2 Hz, 2H),rotomers −59.04 6.95 (d, J = 7.4 Hz, 1H), 6.62 (dd, J = 15.9, 9.0 Hz, &−59.08, 1H), 6.43 (ddd, J = 16.0, 10.0, 7.9 Hz, −68.57 2H), 5.57-5.52(m, 1H), 5.46 (h, J = 7.0 Hz, 1H), 4.13 (p, J = 8.5 Hz, 1H), 2.13 (d, J= 1.3 Hz, 3H), 1.85 (d, J = 1.4 Hz, 3H), 1.70 (d, J = 6.8 Hz, 3H) F9ESIMS ¹H NMR (400 MHz, CDCl₃) δ 7.67 (s, 1H), ¹⁹F NMR (376 MHz, m/z 6027.59 (d, J = 7.9 Hz, 1H), 7.50 (d, J = 8.0 Hz, CDCl₃) δ ([M + H]⁺) 1H),7.41 (s, 2H), 6.75 (t, J = 7.4 Hz, −59.02, −68.56 2H), 6.61 (d, J = 15.9Hz, 1H), 6.43 (dd, J = 15.9, 7.8 Hz, 1H), 5.44 (q, J = 7.2 Hz, 1H),4.17-4.07 (m, 1H), 2.67 (td, J = 7.1, 1.0 Hz, 2H), 2.55 (t, J = 6.9 Hz,2H), 1.70 (d, J = 6.8 Hz, 3H) F10 ESIMS ¹H NMR (400 MHz, CDCl₃) δ 7.66(s, 1H), ¹⁹F NMR (376 MHz, m/z 659 7.57 (d, J = 8.0 Hz, 1H), 7.46 (d, J= 7.9 Hz, CDCl₃) δ ([M + H]⁺) 1H), 7.41 (s, 2H), 6.90 (s, 1H), −59.06,−66.23, 6.72 (d, J = 7.9 Hz, 1H), 6.61 (d, J = 15.9 Hz, −68.57 1H), 6.43(dd, J = 15.9, 7.8 Hz, 1H), 5.43 (h, J = 7.0 Hz, 1H), 4.12 (p, J = 8.5Hz, 1H), 2.30-2.22 (m, 2H), 2.20-2.02 (m, 2H), 1.89 (p, J = 7.4 Hz, 2H),1.68 (d, J = 6.8 Hz, 3H) F11 ESIMS ¹H NMR (400 MHz, CDCl₃) δ 7.66 (s,1H), ¹⁹F NMR (376 MHz, m/z 588 7.57 (d, J = 8.0 Hz, 1H), 7.47 (d, J =8.0 Hz, CDCl₃) δ ([M + H]⁺) 1H), 7.41 (s, 2H), 7.34 (d, J = 7.4 Hz,−58.97, −68.55 1H), 6.88 (d, J = 7.6 Hz, 1H), 6.61 (d, J = 16.0 Hz, 1H),6.44 (dd, J = 15.9, 7.8 Hz, 1H), 5.51 (h, J = 6.9 Hz, 1H), 4.19-4.06 (m,1H), 3.37 (s, 2H), 1.69 (d, J = 6.8 Hz, 3H) F12 ESIMS ¹H NMR (400 MHz,DMSO-d₆) δ 8.71 (d, J = 7.6 Hz, ¹⁹F NMR (376 MHz, m/z 659 1H), 8.31 (d,J = 7.7 Hz, 1H), DMSO- ([M + H]⁺) 7.99 (d, J = 1.6 Hz, 1H), 7.95-7.86(m, d₆) δ −57.83, −65.19, 3H), 7.45 (d, J = 7.9 Hz, 1H), 7.05 (dd, J =15.8, −67.95 9.1 Hz, 1H), 6.86 (d, J = 15.7 Hz, 1H), 5.39 (p, J = 7.3Hz, 1H), 4.86 (p, J = 9.4 Hz, 1H), 2.50 (dt, J = 3.7, 1.9 Hz, 2H),2.43-2.28 (m, 2H), 1.68 (dq, J = 11.6, 6.7 Hz, 2H), 0.88 (t, J = 7.4 Hz,3H) F13 ESIMS ¹H NMR (400 MHz, DMSO-d₆) δ 9.13 (t, J = 5.9 Hz, ¹⁹F NMR(376 MHz, m/z 629 1H), 8.78 (t, J = 6.0 Hz, 1H), DMSO- ([M + H]⁺) 7.98(d, J = 1.6 Hz, 1H), 7.93 (s, 2H), 7.89 (dd, d₆) δ −57.82, −65.21, J =8.0, 1.8 Hz, 1H), 7.45 (d, J = 8.0 Hz, −67.95 1H), 7.06 (dd, J = 15.8,9.1 Hz, 1H), 6.86 (d, J = 15.8 Hz, 1H), 4.85 (q, J = 9.4 Hz, 1H), 4.54(t, J = 5.9 Hz, 2H), 2.61-2.28 (m, 4H) F14 ESIMS ¹H NMR (400 MHz,DMSO-d₆) δ 8.70 (d, J = 7.3 Hz, ¹⁹F NMR (376 MHz, m/z 612 1H), 8.28 (d,J = 7.6 Hz, 1H), DMSO- ([M − H]⁻) 8.00 (d, J = 1.6 Hz, 1H), 7.93 (s,2H), d₆) δ −57.78, −67.93 7.92-7.87 (m, 1H), 7.53 (d, J = 8.0 Hz, 1H),7.06 (dd, J = 15.7, 9.1 Hz, 1H), 6.87 (d, J = 15.7 Hz, 1H), 5.65 (h, J =6.8 Hz, 1H), 4.85 (q, J = 9.5 Hz, 1H), 1.62-1.43 (m, 4H), 1.36 (d, J =6.5 Hz, 3H) F15 ESIMS ¹H NMR (400 MHz, DMSO-d₆) δ 8.72 (d, J = 7.4 Hz,¹⁹F NMR (376 MHz, m/z 617 1H), 8.05 (d, J = 7.5 Hz, 1H), DMSO- ([M −H]⁻) 7.98 (d, J = 1.7 Hz, 1H), 7.93 (s, 2H), d₆) δ −57.81, −67.967.92-7.85 (m, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.05 (dd, J = 15.7, 9.1 Hz,1H), 6.86 (d, J = 15.7 Hz, 1H), 5.58 (h, J = 6.8 Hz, 1H), 4.86 (p, J =9.4 Hz, 1H), 1.97 (d, J = 2.7 Hz, 2H), 1.31 (d, J = 6.5 Hz, 3H), 0.97(s, 9H) F16 ESIMS ¹H NMR (400 MHz, DMSO-d₆) mixture of ¹⁹F NMR (376 MHz,m/z 657 diastereomers δ 8.89-8.72 (m, 1H), DMSO- ([M − H]⁻) 8.53-8.41(m, 1H), 8.01-7.96 (m, 1H), d₆), mixture 7.93 (s, 2H), 7.92-7.86 (m,1H), of 7.51-7.42 (m, 1H), 7.06 (dd, J = 15.8, 9.1 Hz, 1H),diastereomers 6.87 (d, J = 15.7 Hz, 1H), 5.68-5.50 (m, δ −57.84, −67.96,1H), 4.86 (p, J = 9.4 Hz, 1H), −72.25, 2.88-2.70 (m, 1H), 2.46-2.38 (m,1H), −72.26 2.22-2.11 (m, 1H), 1.39-1.28 (m, 3H), 1.11-1.03 (m, 3H) F17ESIMS ¹H NMR (400 MHz, DMSO-d₆) δ 8.70 (d, J = 7.2 Hz, ¹⁹F NMR (376 MHz,m/z 631 1H), 8.16 (d, J = 7.5 Hz, 1H), DMSO- ([M − H]⁻) 7.98 (d, J = 1.8Hz, 1H), 7.96-7.86 (m, d₆) δ −57.80, −67.95 3H), 7.45 (d, J = 8.0 Hz,1H), 7.05 (dd, J = 15.8, 9.1 Hz, 1H), 6.86 (d, J = 15.7 Hz, 1H), 5.55(h, J = 6.7 Hz, 1H), 4.86 (p, J = 9.4 Hz, 1H), 2.11-2.00 (m, 2H),1.47-1.37 (m, 2H), 1.31 (d, J = 6.5 Hz, 3H), 0.86 (s, 9H) F18 ESIMS ¹HNMR (400 MHz, DMSO-d₆) δ 8.71 (d, J = 7.2 Hz, ¹⁹F NMR (376 MHz, m/z 6471H), 8.12 (d, J = 7.5 Hz, 1H), DMSO- ([M + H]⁺) 8.00-7.95 (m, 1H), 7.92(s, 2H), d₆) δ −57.78, −67.95 7.88 (dd, J = 7.9, 1.6 Hz, 1H), 7.45 (d, J= 7.9 Hz, 1H), 7.05 (dd, J = 15.8, 9.1 Hz, 1H), 6.86 (d, J = 15.7 Hz,1H), 5.56 (h, J = 6.7 Hz, 1H), 4.86 (p, J = 9.5 Hz, 1H), 2.04 (t, J =7.4 Hz, 2H), 1.46 (dtd, J = 9.7, 7.5, 4.5 Hz, 2H), 1.32 (d, J = 6.5 Hz,3H), 1.18-1.09 (m, 2H), 0.85 (s, 9H) F19 ESIMS ¹H NMR (400 MHz, DMSO-d₆)δ 8.57 (d, J = 7.3 Hz, ¹⁹F NMR (376 MHz, m/z 603 1H), 7.99 (d, J = 1.6Hz, 1H), DMSO- ([M − H]⁻) 7.92 (s, 2H), 7.89 (dd, J = 8.1, 1.6 Hz, d₆) δ−57.76, −67.95 1H), 7.58 (d, J = 7.7 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H),7.05 (dd, J = 15.8, 9.1 Hz, 1H), 6.86 (d, J = 15.7 Hz, 1H), 5.59 (h, J =6.8 Hz, 1H), 4.86 (p, J = 9.4 Hz, 1H), 1.34 (d, J = 6.5 Hz, 3H), 1.10(s, 9H) F20 ESIMS ¹H NMR (400 MHz, CDCl₃) δ ¹⁹F NMR (376 MHz, m/z 6437.71-7.63 (m, 1H), 7.65-7.53 (m, 1H), 7.47 (d, J = 7.9 Hz, CDCl₃) δ ([M− H]⁻) 1H), 7.41 (s, 2H), 6.66-6.56 (m, −59.32, −62.60, 1H), 6.42 (dd, J= 16.0, 7.8 Hz, 1H), −68.59 6.42 (s, 1H), 4.12 (p, J = 8.8 Hz, 1H),3.73-3.63 (m, 4H), 3.22 (q, J = 9.9 Hz, 2H), 3.13 (s, 3H) F21 ESIMS ¹HNMR (400 MHz, CDCl₃) δ 7.67 (d, J = 1.6 Hz, ¹⁹F NMR (376 MHz, m/z 6291H), 7.59 (dd, J = 7.9, 1.7 Hz, CDCl₃) δ ([M − H]⁻) 1H), 7.45 (d, J =7.9 Hz, 1H), 7.41 (s, 2H), −59.22, −68.59, 6.66-6.57 (m, 1H), 6.43 (dd,J = 15.9, −69.88 7.9 Hz, 1H), 6.18 (s, 1H), 4.12 (p, J = 8.8 Hz, 1H),3.72 (d, J = 3.2 Hz, 4H), 3.25 (q, J = 1.5 Hz, 3H) F22 ESIMS ¹H NMR (400MHz, DMSO-d₆) δ 11.05 (bs, IR (thin film) m/z 615 1H), 8.11 (s, 1H),7.98 (d, J = 8.4 Hz, 1H), 3256, 1698, ([M + H]⁺) 7.92 (s, 2H), 7.79 (s,J = 7.6 Hz, 1H), 1114, 749 7.15 (dd, J = 16.4, 9.6 Hz, 1H), 6.92 (d, J =16.0 Hz, (cm⁻¹) 1H), 4.90-4.83 (m, 1H), 3.10 (s, 3H), 2.50 (s, 2H) F23ESIMS ¹H NMR (400 MHz, DMSO-d₆) δ 11.01 (bs, IR (thin film) m/z 629 1H),8.10 (s, 1H), 7.99 (d, J = 8.4 Hz, 1H), 3436, 1689, ([M + H]⁺) 7.92 (s,2H), 7.68 (s, J = 8.0 Hz, 1H), 1275, 750 7.15 (dd, J = 15.6, 8.8 Hz,1H), 6.92 (d, J = 15.6 Hz, (cm⁻¹) 1H), 4.90-4.83 (m, 1H), 3.11 (s, 3H),2.97 (s, 1H), 2.67-2.58 (m, 3H)

TABLE 4 Structure and Preparation Method for C Series Compounds Prep.according to No. Structure example C113

21 C115

24 C116

26

TABLE 5 Structure and Preparation Method for Exemplified P SeriesCompounds Prep. according No. Structure to example: P1

30 P2

30 P3

30 P4

30 P5

30 P6

30 P7

30 P8

30 P9

30 P10

30 P11

30 P12

30 P13

30 P14

30 P15

30 P16

30 P22

30 P24

30 P25

30 P27

30 P30

19 P33

19 P36

31 P43

31 P47

31 P49

31 P53

30 P54

30

TABLE 6 Analytical Data for Compounds in Table 5 No. Mass (m/z) ¹H NMR¹⁹F NMR/IR P1 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR(thin film) for C₂₃H₁₆Cl₂F₁₀N₂O₂, 8.90 (d, J = 7.3 Hz, 1H), 8.65 (d, J =7.4 Hz, 1678 cm⁻¹ 613.0502; Found, 1H), 8.02-7.97 (m, 1H), 613.0494 7.89(dd, J = 10.3, 7.1 Hz, 3H), 7.45 (d, J = 7.9 Hz, 1H), 7.05 (dd, J =15.8, 9.2 Hz, 1H), 6.86 (d, J = 15.7 Hz, 1H), 5.58 (h, J = 6.8 Hz, 1H),4.83 (p, J = 9.4 Hz, 1H), 3.27 (q, J = 11.3 Hz, 2H), 1.35 (d, J = 6.5Hz, 3H) P2 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR (thinfilm) for C₂₃H₁₇Br₂ClF₉N₂O₂, 8.89 (d, J = 7.4 Hz, 1H), 8.63 (d, J = 7.4Hz, 1675 cm⁻¹ 718.9176; Found, 1H), 8.06 (s, 2H), 8.01-7.97 (m, 718.91811H), 7.93-7.87 (m, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.06 (dd, J = 15.8,9.2 Hz, 1H), 6.85 (d, J = 15.7 Hz, 1H), 5.57 (h, J = 6.8 Hz, 1H), 4.84(p, J = 9.4 Hz, 1H), 3.27 (q, J = 11.3 Hz, 2H), 1.35 (d, J = 6.5 Hz, 3H)P3 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR (thin film)for C₂₃H₁₇Br₂F₉N₂O₂, 8.90 (d, J = 7.4 Hz, 1H), 8.64 (d, J = 7.4 Hz, 1677cm⁻¹ 684.9567; Found, 1H), 8.01-7.97 (m, 1H), 684.9570 7.93-7.88 (m,2H), 7.85 (d, J = 1.7 Hz, 2H), 7.45 (d, J = 7.9 Hz, 1H), 7.06 (dd, J =15.8, 9.2 Hz, 1H), 6.86 (d, J = 15.7 Hz, 1H), 5.58 (h, J = 6.8 Hz, 1H),4.82 (p, J = 9.5 Hz, 1H), 3.27 (q, J = 11.3 Hz, 2H), 1.35 (d, J = 6.5Hz, 3H) P4 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR (thinfilm) for C₂₄H₁₈Br₂ClF₉N₂O₂, 8.89 (d, J = 7.4 Hz, 1H), 8.63 (d, J = 7.4Hz, 1675 cm⁻¹ 674.9679; Found, 1H), 8.01-7.97 (m, 1H), 674.96817.92-7.84 (m, 3H), 7.45 (d, J = 7.9 Hz, 1H), 7.05 (dd, J = 15.8, 9.1 Hz,1H), 6.86 (d, J = 15.7 Hz, 1H), 5.57 (h, J = 6.8 Hz, 1H), 4.85 (p, J =9.2 Hz, 1H), 3.27 (q, J = 11.5 Hz, 2H), 1.35 (d, J = 6.6 Hz, 3H) P5HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR (thin film) forC₂₃H₁₉Cl₂F₇N₂O₂, 8.62-8.54 (m, 2H), 7.84 (d, J = 6.3 Hz, 1672 cm⁻¹559.0785; Found, 2H), 7.45 (d, J = 1.8 Hz, 1H), 559.0794 7.40 (dd, J =8.0, 1.7 Hz, 1H), 7.29 (d, J = 7.9 Hz, 1H), 6.84 (dd, J = 15.7, 9.1 Hz,1H), 6.72 (d, J = 15.7 Hz, 1H), 5.60 (h, J = 6.8 Hz, 1H), 4.80 (p, J =9.4 Hz, 1H), 3.27 (q, J = 11.3 Hz, 2H), 2.33 (s, 3H), 1.35 (d, J = 6.5Hz, 3H) P6 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR (thinfilm) for C₂₃H₁₉BrCl₂F₆N₂O₂, 8.60 (d, J = 7.5 Hz, 1H), 8.57 (d, J = 7.2Hz, 1672 cm⁻¹ 732.9332; Found, 1H), 7.85 (s, 2H), 7.45 (d, J = 1.7 Hz,732.9342 1H), 7.40 (dd, J = 8.0, 1.7 Hz, 1H), 7.29 (d, J = 7.8 Hz, 1H),6.83 (dd, J = 15.7, 9.0 Hz, 1H), 6.72 (d, J = 15.6 Hz, 1H), 5.60 (h, J =6.8 Hz, 1H), 4.81 (p, J = 9.4 Hz, 1H), 3.26 (q, J = 11.3 Hz, 2H), 2.33(s, 3H), 1.35 (d, J = 6.5 Hz, 3H) P7 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500MHz, DMSO-d₆) δ IR (thin film) for C₂₃H₂₁Br₂F₆N₂O₂, 8.59 (d, J = 7.5 Hz,1H), 8.56 (d, J = 7.2 Hz, 1656 cm⁻¹ 630.9850; Found, 1H), 7.89 (t, J =1.7 Hz, 1H), 630.9858 7.82 (d, J = 1.7 Hz, 2H), 7.47-7.43 (m, 1H), 7.40(dd, J = 8.0, 1.7 Hz, 1H), 7.29 (d, J = 7.8 Hz, 1H), 6.83 (dd, J = 15.7,9.1 Hz, 1H), 6.72 (d, J = 15.6 Hz, 1H), 5.60 (h, J = 6.8 Hz, 1H), 4.79(p, J = 9.5 Hz, 1H), 3.27 (q, J = 11.3 Hz, 2H), 2.33 (s, 3H), 1.35 (d, J= 6.5 Hz, 3H) P8 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR(thin film) for C₂₃H₂₀Br₂ClF₆N₂O₂, 8.60 (d, J = 7.5 Hz, 1H), 8.57 (d, J= 7.3 Hz, 1673 cm⁻¹ 664.9458; Found, 1H), 8.03 (s, 2H), 7.45 (d, J = 1.8Hz, 664.9465 1H), 7.41 (dd, J = 8.1, 1.7 Hz, 1H), 7.29 (d, J = 7.9 Hz,1H), 6.84 (dd, J = 15.7, 9.1 Hz, 1H), 6.72 (d, J = 15.7 Hz, 1H), 5.60(h, J = 6.8 Hz, 1H), 4.81 (p, J = 9.5 Hz, 1H), 3.27 (q, J = 11.3 Hz,2H), 2.33 (s, 3H), 1.35 (d, J = 6.5 Hz, 3H) P9 HRMS-ESI [M + H]⁺ calcd¹H NMR (400 MHz, DMSO-d₆) δ IR (thin film) for C₂₄H₁₈Cl₂F₁₀N₂O₂, 8.78(d, J = 7.2 Hz, 1H), 8.41 (d, J = 7.5 Hz, 1667 cm⁻¹ 627.0658; Found,1H), 8.00-7.96 (m, 1H), 627.0662 7.91-7.85 (m, 3H), 7.46 (d, J = 7.9 Hz,1H), 7.05 (dd, J = 15.8, 9.1 Hz, 1H), 6.86 (d, J = 15.8 Hz, 1H), 5.58(h, J = 6.7 Hz, 1H), 4.84 (p, J = 9.4 Hz, 1H), 2.58-2.28 (m, 4H), 1.33(d, J = 6.5 Hz, 3H) P10 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz,DMSO-d₆) δ IR (thin film) for C₂₄H₁₈Br₂ClF₉N₂O₂, 8.77 (d, J = 7.2 Hz,1H), 8.40 (d, J = 7.5 Hz, 1665 cm⁻¹ 732.9332; Found, 1H), 8.06 (s, 2H),7.98 (d, J = 1.7 Hz, 732.9342 1H), 7.92-7.85 (m, 1H), 7.45 (d, J = 8.0Hz, 1H), 7.05 (dd, J = 15.8, 9.2 Hz, 1H), 6.86 (d, J = 15.7 Hz, 1H),5.57 (h, J = 6.7 Hz, 1H), 4.84 (p, J = 9.4 Hz, 1H), 2.52-2.29 (m, 4H),1.33 (d, J = 6.5 Hz, 3H) P11 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz,DMSO-d₆) δ IR (thin film) for C₂₄H₁₉Br₂F₉N₂O₂, 8.78 (d, J = 7.1 Hz, 1H),8.41 (d, J = 7.4 Hz, 1665 cm⁻¹ 698.9723; Found, 1H), 7.98 (d, J = 1.6Hz, 1H), 698.9721 7.93-7.87 (m, 2H), 7.86 (d, J = 1.7 Hz, 2H), 7.45 (d,J = 7.9 Hz, 1H), 7.05 (dd, J = 15.8, 9.2 Hz, 1H), 6.86 (d, J = 15.7 Hz,1H), 5.58 (h, J = 6.8 Hz, 1H), 4.82 (p, J = 9.5 Hz, 1H), 2.57-2.28 (m,4H), 1.33 (d, J = 6.5 Hz, 3H) P12 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500MHz, DMSO-d₆) δ IR (thin film) for C₂₄H₁₉BrCl₂F₉N₂O₂, 8.78 (d, J = 7.2Hz, 1H), 8.41 (d, J = 7.5 Hz, 1666 cm⁻¹ 688.9836; Found, 1H), 8.00-7.96(m, 1H), 7.88 (s, 688.9845 3H), 7.46 (d, J = 7.9 Hz, 1H), 7.05 (dd, J =15.7, 9.1 Hz, 1H), 6.86 (d, J = 15.7 Hz, 1H), 5.58 (h, J = 6.8 Hz, 1H),4.85 (p, J = 9.4 Hz, 1H), 2.54-2.29 (m, 4H), 1.33 (d, J = 6.5 Hz, 3H)P13 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR (thin film)for C₂₄H₂₁Cl₂F₇N₂O₂, 8.47 (d, J = 7.3 Hz, 1H), 8.35 (d, J = 7.2 Hz, 1655cm⁻¹ 573.0941; Found, 1H), 7.84 (d, J = 6.2 Hz, 2H), 573.0911 7.45 (d, J= 1.8 Hz, 1H), 7.42-7.37 (m, 1H), 7.29 (d, J = 7.8 Hz, 1H), 6.84 (dd, J= 15.7, 9.1 Hz, 1H), 6.72 (d, J = 15.7 Hz, 1H), 5.61 (h, J = 6.7 Hz,1H), 4.80 (p, J = 9.4 Hz, 1H), 2.58-2.21 (m, 7H), 1.33 (d, J = 6.5 Hz,3H) P14 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR (thinfilm) for C₂₄H₁₈Br₂ClF₉N₂O₂, 8.46 (d, J = 7.3 Hz, 1H), 8.33 (d, J = 7.2Hz, 1660 cm⁻¹ 678.9615; Found, 1H), 8.03 (s, 2H), 7.44 (d, J = 1.7 Hz,678.9623 1H), 7.39 (dd, J = 8.0, 1.7 Hz, 1H), 7.29 (d, J = 7.8 Hz, 1H),6.83 (dd, J = 15.7, 9.1 Hz, 1H), 6.72 (d, J = 15.6 Hz, 1H), 5.60 (h, J =6.8 Hz, 1H), 4.81 (p, J = 9.5 Hz, 1H), 2.49-2.42 (m, 2H), 2.42-2.28 (m,5H), 1.33 (d, J = 6.5 Hz, 3H) P15 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500MHz, DMSO-d₆) δ IR (thin film) for C₂₄H₂₂Br₂F₆N₂O₂, 8.48 (d, J = 7.3 Hz,1H), 8.35 (d, J = 7.2 Hz, 1660 cm⁻¹ 645.0006; Found, 1H), 7.89 (t, J =1.8 Hz, 1H), 645.0004 7.82 (d, J = 1.8 Hz, 2H), 7.45 (d, J = 1.7 Hz,1H), 7.41-7.37 (m, 1H), 7.29 (d, J = 7.9 Hz, 1H), 6.82 (dd, J = 15.7,9.1 Hz, 1H), 6.72 (d, J = 15.6 Hz, 1H), 5.61 (h, J = 6.7 Hz, 1H), 4.79(p, J = 9.5 Hz, 1H), 2.56-2.28 (m, 7H), 1.33 (d, J = 6.5 Hz, 3H) P16HRMS-ESI [M + H]⁺ calcd ¹H NMR (400 MHz, DMSO-d₆) δ IR (thin film) forC₂₄H₂₁BrCl₂F₆N₂O₂, 8.47 (d, J = 7.3 Hz, 1H), 8.34 (d, J = 7.2 Hz, 1660cm⁻¹ 632.0118; Found, 1H), 7.85 (s, 2H), 7.50-7.42 (m, 635.0128 1H),7.40 (dd, J = 7.9, 1.7 Hz, 1H), 7.29 (d, J = 7.9 Hz, 1H), 6.83 (dd, J =15.7, 8.9 Hz, 1H), 6.72 (d, J = 15.7 Hz, 1H), 5.60 (h, J = 6.8 Hz, 1H),4.82 (p, J = 9.4 Hz, 1H), 2.61-2.22 (m, 7H), 1.33 (d, J = 6.5 Hz, 3H)P22 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR (thin film)for C₂₃H₂₀Cl₃F₆N₂O₂, 8.59 (d, J = 7.5 Hz, 1H), 8.56 (d, J = 7.3 Hz, 1671cm⁻¹ 577.0463; Found, 1H), 7.89 (s, 2H), 7.45 (d, J = 1.8 Hz, 577.04701H), 7.40 (dd, J = 8.0, 1.7 Hz, 1H), 7.29 (d, J = 7.9 Hz, 1H), 6.84 (dd,J = 15.7, 9.1 Hz, 1H), 6.73 (d, J = 15.7 Hz, 1H), 5.60 (h, J = 6.8 Hz,1H), 4.83 (p, J = 9.4 Hz, 1H), 3.26 (q, J = 11.3 Hz, 2H), 2.33 (s, 3H),1.35 (d, J = 6.5 Hz, 3H) P24 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz,DMSO-d₆) δ IR (thin film) for C₂₂H₁₇BrCl₃F₆N₂O₂, 8.84 (dd, J = 7.6, 1.6Hz, 1H), 8.63 (d, J = 7.6 Hz, 1675 cm⁻¹ 640.9414; Found, 1H), 7.89 (s,2H), 7.63 (d, J = 8.2 Hz, 640.9414 1H), 7.58-7.50 (m, 2H), 6.90 (dd, J =15.7, 9.1 Hz, 1H), 6.76 (d, J = 15.7 Hz, 1H), 5.64 (h, J = 6.8 Hz, 1H),4.84 (p, J = 9.3 Hz, 1H), 3.29 (q, J = 11.3 Hz, 2H), 1.38 (d, J = 6.5Hz, 3H) P25 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR (thinfilm) for C₂₄H₂₁Cl₃F₆N₂O₂, 8.47 (d, J = 7.3 Hz, 1H), 8.34 (d, J = 7.2Hz, 1656 cm⁻¹ 589.0646; Found, 1H), 7.89 (s, 2H), 7.45 (d, J = 1.7 Hz,589.0657 1H), 7.43-7.37 (m, 1H), 7.29 (d, J = 7.8 Hz, 1H), 6.84 (dd, J =15.7, 9.1 Hz, 1H), 6.73 (d, J = 15.7 Hz, 1H), 5.60 (h, J = 6.7 Hz, 1H),4.83 (p, J = 9.4 Hz, 1H), 2.56-2.28 (m, 7H), 1.33 (d, J = 6.5 Hz, 3H)P27 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR (thin film)for C₂₃H₁₉BrCl₃F₆N₂O₂, 8.70 (dd, J = 7.2, 1.9 Hz, 1H), 8.37 (d, J = 7.6Hz, 1666 cm⁻¹ 654.9571; Found, 1H), 7.89 (s, 2H), 7.62 (d, J = 8.3 Hz,654.9582 1H), 7.55 (t, J = 1.9 Hz, 1H), 7.52 (ddd, J = 8.0, 5.3, 2.2 Hz,1H), 6.89 (ddd, J = 15.8, 9.1, 1.8 Hz, 1H), 6.75 (d, J = 15.6 Hz, 1H),5.62 (h, J = 6.7 Hz, 1H), 4.83 (p, J = 9.5 Hz, 1H), 2.56-2.43 (m, 2H),2.42-2.29 (m, 2H), 1.35 (d, J = 6.5 Hz, 3H) P30 ESIMS 657 Mixture ofdiastereomers: ¹H NMR Mixture of ([M − H]⁻) (400 MHz, CDCl₃) δ 7.67-7.63(m, diastereomers: 1H), 7.59-7.51 (m, 1H), (Major) ¹⁹F 7.46-7.40 (m,3H), 7.18-7.04 (m, 2H), 6.61 (d, NMR (376 MHz, J = 15.9 Hz, 1H), 6.42(dd, J = 16.0, CDCl₃) δ 7.9 Hz, 1H), 5.40 (hept, J = 7.0 Hz, −59.09,−64.97, 1H), 4.12 (p, J = 8.6 Hz, 1H), −68.59; 2.71-2.45 (m, 2H),2.20-1.97 (m, 1H), (Minor) 19F 1.71-1.61 (m, 3H), 1.24-1.19 (m, NMR (376MHz, 3H) CDCl₃) δ −59.11, −64.96, −68.60 P33 ESIMS 657 ¹H NMR (400 MHz,CDCl₃) δ 7.64 (d, J = 1.7 Hz, ¹⁹F NMR (376 MHz, ([M − H]⁻) 1H), 7.55(dd, J = 8.0, 1.7 Hz, CDCl₃) δ 1H), 7.45-7.40 (m, 3H), 7.30 (d, −59.12,−68.60, J = 7.3 Hz, 1H), 7.23 (d, J = 7.5 Hz, −74.48 1H), 6.61 (d, J =15.9 Hz, 1H), 6.42 (dd, J = 15.9, 7.9 Hz, 1H), 5.46 (h, J = 7.0 Hz, 1H),4.20-4.03 (m, 1H), 1.66 (d, J = 6.7 Hz, 3H), 1.38 (s, 6H) P36 HRMS-ESI[M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR (thin film) forC₂₃H₁₉Cl₃F₆N₂O₃S, 8.92-8.86 (m, 1H), 8.64-8.56 (m, 1H), 1671 cm⁻¹625.0132; Found, 7.99 (s, 1H), 7.91 (d, J = 16.8 Hz, 625.0136 3H),7.50-7.45 (m, 1H), 7.06 (dd, J = 15.7, 9.1 Hz, 1H), 6.87 (d, J = 15.7Hz, 1H), 5.65-5.56 (m, 1H), 4.86 (p, J = 9.4 Hz, 1H), 3.74-3.59 (m, 2H),2.65-2.61 (m, 3H), 1.39-1.31 (m, 3H) P43 HRMS-ESI [M + H]⁺ calcd ¹H NMR(500 MHz, DMSO-d₆) δ IR (thin film) for C₂₃H₁₉Cl₃F₆N₂O₄S, 8.93 (d, J =7.5 Hz, 1H), 8.72 (d, J = 7.4 Hz, 1677 cm⁻¹ 641.0082; Found, 1H),8.03-7.96 (m, 1H), 7.91 (d, 641.0089 J = 14.8 Hz, 3H), 7.47 (d, J = 7.9Hz, 1H), 7.06 (dd, J = 15.8, 9.1 Hz, 1H), 6.87 (d, J = 15.7 Hz, 1H),5.60 (h, J = 6.8 Hz, 1H), 4.86 (p, J = 9.4 Hz, 1H), 4.15 (d, J = 14.2Hz, 1H), 4.06-4.02 (m, 1H), 3.12 (s, 3H), 1.35 (d, J = 6.5 Hz, 3H) P47HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR (thin film) forC₂₄H₂₁Cl₃F₆N₂O₄S, 8.77 (d, J = 7.1 Hz, 1H), 8.46 (d, J = 7.4 Hz, 1670cm⁻¹ 655.0238; Found, 1H), 7.98 (d, J = 1.7 Hz, 1H), 655.026 7.94-7.86(m, 3H), 7.47 (d, J = 7.9 Hz, 1H), 7.05 (dd, J = 15.8, 9.1 Hz, 1H), 6.86(d, J = 15.7 Hz, 1H), 5.58 (h, J = 6.7 Hz, 1H), 4.86 (p, J = 9.4 Hz,1H), 3.35-3.29 (m, 2H), 2.98 (s, 3H), 2.63-2.52 (m, 2H), 1.33 (d, J =6.5 Hz, 3H) P49 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ forC₂₄H₂₁Cl₃F₆N₂O₃S, 8.80-8.74 (m, 1H), 8.45-8.39 (m, 1H), 639.0289; Found,7.99-7.97 (m, 1H), 7.90 (d, J = 22.0 Hz, 639.0299 3H), 7.47 (d, J = 7.9Hz, 1H), 7.05 (dd, J = 15.7, 9.1 Hz, 1H), 6.87 (d, J = 15.7 Hz, 1H),5.58 (h, J = 6.7 Hz, 1H), 4.86 (p, J = 9.4 Hz, 1H), 3.06-2.97 (m, 1H),2.81 (ddt, J = 11.3, 7.1, 5.5 Hz, 1H), 2.53 (s, 3H), 2.52-2.51 (m, 2H),1.33 (d, J = 6.5 Hz, 3H) P53 HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz,DMSO-d₆) δ IR (thin film) for C₂₄H₂₁Cl₃F₆N₂O₂S, 8.74 (d, J = 7.2 Hz,1H), 8.27 (d, J = 7.5 Hz, 1662 cm⁻¹ 623.034; Found 1H), 7.98 (d, J = 1.9Hz, 1H), 623.0342 7.92 (s, 2H), 7.89 (d, J = 7.8 Hz, 1H), 7.46 (d, J =7.9 Hz, 1H), 7.05 (dd, J = 15.7, 9.1 Hz, 1H), 6.86 (d, J = 15.7 Hz, 1H),5.57 (h, J = 6.8 Hz, 1H), 4.86 (p, J = 9.4 Hz, 1H), 2.65 (t, J = 7.0 Hz,2H), 2.45-2.31 (m, 2H), 2.06 (s, 3H), 1.32 (d, J = 6.5 Hz, 3H) P54HRMS-ESI [M + H]⁺ calcd ¹H NMR (500 MHz, DMSO-d₆) δ IR (thin film) forC₂₃H₁₉Cl₃F₆N₂O₂S; 8.81 (d, J = 7.4 Hz, 1H), 8.30 (d, J = 7.6 Hz, 1664cm⁻¹ 609.0183; 1H), 8.01-7.97 (m, 1H), Found, 609.0188 7.94-7.87 (m,3H), 7.47 (d, J = 7.9 Hz, 1H), 7.05 (dd, J = 15.7, 9.1 Hz, 1H), 6.86 (d,J = 15.7 Hz, 1H), 5.59 (h, J = 6.8 Hz, 1H), 4.86 (p, J = 9.4 Hz, 1H),3.09 (s, 2H), 2.10 (s, 3H), 1.34 (d, J = 6.5 Hz, 3H).

TABLE 7 Structure and Preparation Method for FC Series Compounds Prep.according to No. Structure example: FC1

30 FC2

30

TABLE 8 Analytical Data for Compounds in Table 7 No. Mass (m/z) ¹H NMR¹⁹F NMR/IR FC1 HRMS-ESI [M + H]⁺ calcd Rotomers: ¹H NMR (400 MHz, DMSO-Rotomers: ¹⁹F for C₂₃H₂₀Cl₃F₆N₂O₂; d₆) δ 8.63 (d, J = 7.2 Hz, 1H), NMR(376 MHz, 575.0489; Found, 8.29 (d, J = 7.1 Hz, 1H), 7.88 (s, 2H),CDCl₃) δ 575.0490 7.82 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 8.4 Hz, −66.76,−68.68 2H), 6.93-6.88 (m, 1H), 6.77 (d, J = 15.7 Hz, 1H), 5.63 (h, J =6.7 Hz, 1H), 4.82 (h, J = 9.2 Hz, 1H), 2.47-2.39 (m, 1H), 2.39-2.27 (m,2H), 1.33 (d, J = 6.5 Hz, 3H) FC2 HRMS-ESI [M + H]⁺ calcd Rotomers: ¹HNMR (400 MHz, CDCl₃) δ ¹⁹F NMR (376 MHz, for C₂₂H₁₈Cl₃F₆N₂O₂; 8.51 (d, J= 8.1 Hz, 1H), 8.37 (d, J = 7.9 Hz, CDCl₃) δ 561.0333; Found, 1H), 7.76(d, J = 8.1 Hz, 2H), −62.90, −65.78, 561.0330 7.37 (d, J = 2.4 Hz, 2H),−68.73 7.33-7.28 (m, 2H), 6.64-6.51 (m, 1H), 6.41-6.29 (m, 1H), 6.09 (q,J = 8.3, 7.7 Hz, 1H), 4.17-3.97 (m, 1H), 3.20-3.10 (m, 2H), 1.54 (d, J =6.5 Hz, 3H)

BAW & CL Rating Table % Control (or Mortality) Rating 50-100 A More than0-Less than 50 B Not Tested C No activity noticed in this bioassay D

GPA & YFM Rating Table % Control (or Mortality) Rating 80-100 A Morethan 0-Less than 80 B Not Tested C No activity noticed in this bioassayD

TABLE ABC Assay Results (F) Insect species No. BAW CL GPA YFM F1 A A C CF2 A A D A F3 A A C A F4 A A C A F5 A A C A F6 A A C A F7 A A C A F8 A AC A F9 A A C A F10 A A C A F11 A A C A F12 A A C A F13 A A C C F14 A A CA F15 A A C A F16 A A C A F17 A A C A F18 A A C A F19 A A C A F20 A A CA F21 A A C B F22 A A C A F23 A A C A

TABLE ABCD Assay Results (C) Insect species No. BAW CL GPA YFM C113 A AD A C115 A D C C C116 A A C A

TABLE ABCDE Assay Results (P) Insect species No. BAW CL GPA YFM P1 A A CC P2 A A C A P3 A A C B P4 A A C A P5 A A C A P6 A A C A P7 A A C A P8 AA C C P9 A A C C P10 A A C A P11 A A C A P12 A A C A P13 A A C A P14 A AC A P15 A A C C P16 A A C C P22 A A C C P24 A A C D P25 A A C C P27 A AC B P30 A A C C P33 A A C A P36 A A D C P43 A A C C P47 A A C C P49 A AB C P53 A A C C P54 A A C C

Data

Bioassays on BAW and CL were conducted according to the proceduresoutlined in Example A: Bioassays on Beet Armyworm (“BAW”) and CabbageLooper (“CL”) using the following concentrations: 5, 0.5, and 0.05μg/cm². The results are indicated in Table CD1.

TABLE CD1

5 0.5 0.05 μg/cm² μg/cm² μg/cm² No. R10 R14 BAW CL BAW CL BAW CL FC1^(†)H CH₂CH₂CF₃   13* 71 0 0 0 0 P25 CH₃ CH₂CH₂CF₃ 100 100 100 100 100 100P27 Br CH₂CH₂CF₃   7 100 0 7 0 0 F1 CF₃ CH₂CH₂CF₃ 100 100 100 100 100 97FC2 H CH₂CF₃   0 0 0 0 0 0 P22 CH₃ CH₂CF₃ 100 100 100 100 25 63 P24 BrCH₂CF₃  87 100 7 19 0 6 F2 CF₃ CH₂CF₃ 100 100 100 100 100 100^(†)Compound 30% pure. *Percent control (or mortality)

We claim:
 1. A molecule having the following formula

wherein: (a) R1, R2, R3, R4, and R5, are, each independently, H, F, Cl,Br, I, CN, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl, (C₁-C₆)alkoxy, or(C₁-C₆)haloalkoxy; (b) R6 is (C₁-C₆)haloalkyl; (c) R7 is H; (d) R8 is H,(C₁-C₆)alkyl, or (C₁-C₆)haloalkyl; (e) R9 is H, F, Cl, Br, I,(C₁-C₆)alkyl, or (C₁-C₆)haloalkyl; (f) R10 is F, Cl, Br, I,(C₁-C₆)alkyl, or (C₁-C₆)haloalkyl; (g) R11 and R12 are, eachindependently, H, F, Cl, Br, I, (C₁-C₆)alkyl, or (C₁-C₆)haloalkyl; (h) Lis (1) a linker that is a bond connecting the two nitrogen atoms, or (2)a (C₁-C₆)alkyl that is optionally substituted with one or moresubstituents, wherein each substituent is independently selected from F,Cl, Br, I, CN, OH, oxo, (C₁-C₆)alkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl,S(O)₂(C₁-C₆)alkyl, and N((C₁-C₆)alkyl)₂ wherein each (C₁-C₆)alkyl isindependently selected, and wherein each said alkyl or alkoxy has one ormore substituents independently selected from H, F, Cl, Br, and I; (i)R13 is (1) an H, or (2) a (C₁-C₆)alkyl that is optionally substitutedwith one or more substituents, wherein each substituent is independentlyselected from F, Cl, Br, I, CN, OH, oxo, (C₁-C₆)alkoxy, S(C₁-C₆)alkyl,S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, and N((C₁-C₆)alkyl)₂ wherein each(C₁-C₆)alkyl is independently selected, and wherein each said alkyl oralkoxy has one or more substituents independently selected from H, F,Cl, Br, and I; and (j) R14 is independently selected from (C₁-C₈)alkyl,(C₁-C₈)haloalkyl, (C₃-C₈)cycloalkyl, (C₂-C₈)alkenyl, or (C₂-C₈)alkynyl,wherein each said alkyl, haloalkyl, cycloalkyl, alkenyl, and alkynyl hasone or more substituents selected from F, Cl, Br, I, CN, NO₂, OH, oxo,(C₁-C₆)alkoxy, S(C₁-C₆)alkyl, S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, andN((C₁-C₆)alkyl)₂ wherein each (C₁-C₆)alkyl is independently selected,and wherein each said alkyl or alkoxy has one or more substituentsindependently selected from H, F, Cl, Br, and I.
 2. A molecule accordingto claim 1 wherein: (a) R1 is H; (b) R2 is H, F, Cl, or Br; (c) R3 is H,F, Cl, or Br; (d) R4 is H, F, Cl, or Br; (e) R5 is H; (f) R6 is(C₁-C₈)haloalkyl; (g) R7 is H; (h) R8 is H; (i) R9 is H; (j) R10 isselected from a group consisting of F, Cl, Br, I, (C₁-C₆)alkyl, and(C₁-C₆)haloalkyl; (k) R11 is H; (l) R12 is H; (m) L is (1) a linker thatis bond connecting the two nitrogen atoms, or (2) a (C₁-C₆)alkyl; (n)R13 is (1) an H, or (2) a (C₁-C₈)alkyl; (o) R14 is independentlyselected from (C₁-C₈)alkyl, (C₁-C₈)haloalkyl, (C₃-C₈)cycloalkyl,(C₂-C₈)alkenyl, or (C₂-C₈)alkynyl, wherein each said alkyl, haloalkyl,cycloalkyl, alkenyl, and alkynyl has one or more substituents selectedfrom F, Cl, Br, I, CN, NO₂, OH, oxo, (C₁-C₆)alkoxy, S(C₁-C₆)alkyl,S(O)(C₁-C₆)alkyl, S(O)₂(C₁-C₆)alkyl, and N((C₁-C₆)alkyl)₂ wherein each(C₁-C₆)alkyl is independently selected, and wherein each said alkyl oralkoxy has one or more substituents independently selected from H, F,Cl, Br, and I.
 3. A molecule according to claim 1 wherein: (a) R1 is H;(b) R2 is Cl or Br; (c) R3 is H, F, Cl, or Br; (d) R4 is Cl or Br; (e)R5 is H; (f) R6 is (C₁-C₈)haloalkyl; (g) R7 is H; (h) R8 is H; (i) R9 isH; (j) R10 is Br, (C₁-C₈)alkyl, (C₁-C₈)haloalkyl; (k) R11 is H; (l) R12is H; (m) L is (1) a linker that is bond connecting the two nitrogenatoms, or (2) a (C₁-C₆)alkyl; (n) R13 is (1) an H, or (2) a(C₁-C₈)alkyl; (o) R14 is (C₁-C₈)alkyl, (C₁-C₈)haloalkyl,(C₃-C₅)cycloalkyl, or (C₂-C₈)alkenyl, wherein each said alkyl orcycloalkyl is substituted with CN, SCH₃, S(O)CH₃, or S(O)₂CH₃.
 4. Amolecule according to claim 1 wherein said molecule is selected from oneof the following molecules No. Structure F1

F2

F3

F4

F5

F6

F7

F8

F9

F10

F11

F12

F13

F14

F15

F16

F17

F18

F19

F20

F21

F22

F23


5. A molecule according to claim 1 wherein said molecule is selectedfrom one of the following molecules No. Structure P1

P2

P3

P4

P5

P6

P7

P8

P9

P10

P11

P12

P13

P14

P15

P16

P17

P18

P19

P20

P21

P22

P23

P24

P25

P26

P27

P28

P29

P30

P31

P32

P33

P34

P35

P36

P37

P38

P39

P40

P41

P42

P43

P44

P45

P46

P47

P48

P49

P50

P51

P52

P53

P54


6. A pesticidal composition comprising a molecule according to claim 1and further comprising one or more compounds having a mode of actionselected from: Acetylcholinesterase (AChE) inhibitors; GABA-gatedchloride channel antagonists; Sodium channel modulators; Nicotinicacetylcholine (nAChR) agonists; Nicotinic acetylcholine receptor (nAChR)allosteric activators; Chloride channel activators; Juvenile hormonemimics; Miscellaneous non-specific (multi-site) inhibitors; Selectivehomopteran feeding blockers; Mite growth inhibitors; Microbialdisruptors of insect midgut membranes; Inhibitors of mitochondrial ATPsynthase; Uncouplers of oxidative phosphorylation via disruption of theproton gradient; Nicotinic acetylcholine receptor (nAChR) channelblockers; Inhibitors of chitin biosynthesis, type 0; Inhibitors ofchitin biosynthesis, type 1; Moulting disruptor, Dipteran; Ecdysonereceptor agonists; Octopamine receptor agonists; Mitochondrial complexIII electron transport inhibitors; Mitochondrial complex I electrontransport inhibitors; Voltage-dependent sodium channel blockers;Inhibitors of acetyl CoA carboxylase; Mitochondrial complex IV electrontransport inhibitors; Mitochondrial complex II electron transportinhibitors; and Ryanodine receptor modulators.
 7. A process comprisingapplying a pesticidal composition comprising a molecule according toclaim 1 to a locus to control a pest, in a sufficient amount to controlsaid pest.